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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (1768)

ProteinN (482)

NSP5 (390)

ComplexRdRp (224)

ProteinE (128)


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    Virus capture facilitates a sensitive viral diagnosis for pathogens including SARS-CoV-2

    Authors: Claudia Wylezich; Sten Calvelage; Kore Schlottau; Ute Ziegler; Anne Pohlmann; Dirk Höper; Martin Beer

    doi:10.21203/rs.3.rs-276400/v1 Date: 2021-02-26 Source: ResearchSquare

    When new viruses emerge, early detection is critical, but the detection of pathogens in clinical and environmental samples using high-throughput sequencing is often hampered by large amounts of background material. Enormous sequencing depth can be necessary to gain sufficient information to identify a certain pathogen. Now, a study demonstrates a new method to improve the sensitivity of viral diagnosis. Combining high-throughput sequencing with in-solution virus capture, researchers compiled a virus genome dataset for the design of a RNA-baits panel. The panel, called VirBaits, consists of about 178,000 RNA-baits based on over 18,000 complete viral genomes, targeting 35 epizootic and zoonotic viruses, including SARS-CoV-2. In a test of complex samples, viruses with both DNA and RNA genomes were enriched by anywhere from 10-fold to 10,000-fold, with enriched viruses having at least 72% overall identity shared with the viruses in the bait set. Although the cost and risk of cross-contamination remain concerns for this method, the VirBaits approach represents a promising technique for improving the sensitivity of viral diagnosis in complex samples, enabling the rapid detection of emerging pathogens.

    Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings

    Authors: Meredith Smith Muller; Srijana Bhattarai Chhetri; Christopher Basham; Tyler Rapp; Feng-Chang Lin; Kelly Lin; Daniel Westreich; Carla Cerami; Jonathan J. Juliano; Jessica T Lin

    doi:10.1101/2021.02.18.21251999 Date: 2021-02-25 Source: medRxiv

    Background: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods. Methods: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both standard polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into either viral transport media or an RNA stabilization agent. Quantitative SARS-CoV-2 viral detection by RT-qPCR was compared to that obtained by nasopharyngeal sampling as the reference standard. Pooling specimens in the lab versus pooling swabs at the point of collection was also evaluated. Results: Among 275 participants, flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), mostly missing those with low viral load (<10^3 viral copies/uL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into an RNA stabilizer, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. Pooling sample specimens or swabs both successfully detected samples >102 viral copies/uL. Conclusions: Nasal swabs are likely adequate for clinical diagnosis of acute infections MESHD to help expand testing capacity in resource-constrained settings. When collected into an RNA preservative that also inactivates infectious virus, nasal swabs yielded quantitative viral loads approximating those obtained by nasopharyngeal sampling.

    The United Kingdom Research study into Ethnicity And COVID-19 MESHD outcomes in Healthcare workers (UK-REACH): Protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings

    Authors: Katherine Woolf; Carl Melbourne; Luke Bryant; Anna Louise Guyatt; Ian Christopher McManus; Amit Gupta; Robert C Free; Laura Nellums; Sue Carr; Catherine John; Christopher A Martin; Louise V Wain; Laura J Gray; Claire Garwood; Vishant Modhwadia; Keith Abrams; Martin D Tobin; Kamlesh Khunti; Manish Pareek; - UK-REACH Study Collaborative Group

    doi:10.1101/2021.02.23.21251975 Date: 2021-02-25 Source: medRxiv

    Introduction The COVID-19 pandemic MESHD has resulted in significant morbidity and mortality, and has devastated economies in many countries. Amongst the groups identified as being at increased risk from COVID-19 MESHD are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests HCWs from ethnic minority groups are at increased risk of adverse COVID-19 MESHD-related physical and mental health outcomes. To date there has been no large-scale analysis of these risks in UK healthcare workers or ancillary workers in healthcare settings, stratified by ethnicity or occupation type, and adjusted for potential confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 MESHD outcomes in Healthcare workers). Methods and analysis A baseline questionnaire with follow-up questionnaires at 4 and 8 months will be administered to a national cohort of UK healthcare workers and ancillary workers in healthcare settings, and those registered with UK healthcare regulators. With consent, data will be linked to health records, and participants followed up for 25 years. Univariate associations between ethnicity and primary outcome measures (clinical COVID-19 MESHD outcomes, and physical and mental health) and key confounders/explanatory variables will be tested, followed by multivariable analyses to test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables, with interactions included as appropriate. Using follow-up data, multilevel models will be used to model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings. Ethics and dissemination. The study is approved by Health Research Authority (reference 20/ HRA MESHD/4718), and carries minimal risk to participants. We aim to manage the small risk of participant distress due to being asked questions on sensitive topics by clearly indicating on the participant information sheet that the questionnaire covers sensitive topics and that participants are under no obligation to answer these, or indeed any other, questions, and by providing links to support organisations. Results will be disseminated with reports to Government and papers uploaded to pre-print servers and submitted to peer reviewed journals. Registration details. Trial ID: ISRCTN11811602

    Outcomes of Percutaneous Tracheostomy for Patients with SARS-CoV-2 Respiratory Failure MESHD

    Authors: Jason M Arnold; Catherine A Gao; Elizabeth Malsin; Kristy Todd; A. Christine Argento; Michael Cuttica; John M Coleman III; Richard G Wunderink; Sean B Smith; - NU COVID Investigators

    doi:10.1101/2021.02.23.21252231 Date: 2021-02-25 Source: medRxiv

    Background: SARS-CoV-2 can cause severe respiratory failure MESHD leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2 at our tertiary care, urban teaching hospital. Methods: We reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and ICU and hospital lengths of stay (LOS) in SARS-CoV-2 patients who received tracheostomies. Early tracheostomy was considered <14 days of ventilation. Medians with interquartile ranges (IQR) were calculated and compared with Wilcoxon rank sum, Spearman correlation, Kruskal-Wallis, and regression modeling. Results: From March 2020 to January 2021, our center had 370 patients intubated for SARS-CoV-2, and 59 (16%) had percutaneous bedside tracheostomy. Median time from intubation to tracheostomy was 19 (IQR 17 - 24) days. Demographics and comorbidities were similar between early and late tracheostomy MESHD, but early tracheostomy was associated with shorter ICU LOS and a trend towards shorter ventilation. To date, 34 (58%) of patients have been decannulated, 17 (29%) before hospital discharge; median time to decannulation was 24 (IQR 19-38) days. Decannulated patients were younger (56 vs 69 years), and in regression analysis, pneumothorax was associated was associated with lower decannulation rates (OR 0.05, 95CI 0.01 - 0.37). No providers developed symptoms or tested positive for SARS-CoV-2. Conclusions: Tracheostomy is a safe and reasonable procedure for patients with prolonged SARS-CoV-2 respiratory failure MESHD. We feel that tracheostomy enhances care for SARS-CoV-2 since early tracheostomy appears associated with shorter duration of critical care, and decannulation rates appear high for survivors.

    Household secondary attack rate of COVID-19 MESHD by household size and index case characteristics

    Authors: Semra Tibebu; Kevin A Brown; Nick Daneman; Lauren A Paul; Sarah A Buchan

    doi:10.1101/2021.02.23.21252287 Date: 2021-02-25 Source: medRxiv

    In this population-wide study in Ontario, Canada, we investigated the household secondary attack rate ( SAR HGNC) to understand its relationship to household size and index case characteristics. We identified all patients with confirmed COVID-19 MESHD between July 1 and November 30, 2020. Cases within households were matched based on reported residential address; households were grouped based on the number of household contacts. The majority of households (68.2%) had a SAR HGNC of 0%, while 3,442 (11.7%) households had a SAR HGNC [≥]75%. Overall household SAR HGNC was 19.5% and was similar across household sizes, but varied across index case characteristics. Households where index cases had longer delays between symptom onset and test seeking, households with older index cases, households with symptomatic index cases, and larger households located in diverse neighborhoods, were associated with greater household SAR HGNC. Our findings present characteristics associated with greater household SARs and proposes immediate testing as a method to reduce household transmission and incidence of COVID-19 MESHD.

    A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York

    Authors: Medini K Annavajhala; Hiroshi Mohri; Jason E Zucker; Zizhang Sheng; Pengfei Wang; Angela Gomez-Simmonds; David D Ho; Anne-Catrin Uhlemann

    doi:10.1101/2021.02.23.21252259 Date: 2021-02-25 Source: medRxiv

    Recent months have seen surges of SARS-CoV-2 infection MESHD across the globe along with considerable viral evolution. Extensive mutations in the spike protein PROTEIN of variants B.1.1.7, B1.351, and P.1 HGNC have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February MESHD, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

    The differential impact of the COVID-19 MESHD epidemic on Medicaid expansion and non-expansion states

    Authors: Muhammad Ragaa Hussein; Islam Morsi; Engy A. Awad; Dina Fayed; Thamer AlSulaiman; Mohamed Fouad Habib; John R. Herbold

    doi:10.1101/2021.02.23.21252296 Date: 2021-02-25 Source: medRxiv

    Medicaid expansion is a federally-funded program to expand health care access and coverage to economically challenged populations by increasing eligibility to Medicaid enrollment and investing in public health preventive services in the individual states. Yet, when the COVID-19 MESHD epidemic plagued the country, fourteen states were practicing their chosen decision not to enact the Medicaid expansion policy. We examined the consequences of this nationwide split in Medicaid design on the spread of the COVID-19 MESHD epidemic between the expansion and non-expansion states. Our study shows that, on average, the expansion states had 217.56 fewer confirmed COVID-19 MESHD cases per 100,000 residents than the non-expansion states [-210.41; 95%CI (-411.131) - (-2.05); P<0.05]. Also, the doubling time of COVID-19 MESHD cases in Medicaid expansion states was longer than that of non-expansion states by an average of 1.68 days [1.6826; 95%CI 0.4035-2.9617; P<0.05]. These findings suggest that proactive investment in public health preparedness was an effective protective policy measure in this crisis, unsurpassed by the benefits of COVID-19 MESHD emergency plans and funds. The study findings could be relevant to policymakers and healthcare strategists in non-expansion states considering their states' preparations for such public health crises.

    Clinical evaluation of the molecular-based BD SARS-CoV-2/ Flu HGNC for the BD MAX™ System

    Authors: Sonia Paradis; Elizabeth Lockamy; Charles K Cooper; Stephen Young

    doi:10.1101/2021.02.23.21251915 Date: 2021-02-25 Source: medRxiv

    Efficient and accurate assays for the differential diagnosis of COVID-19 MESHD and/or influenza ( flu HGNC) could facilitate optimal treatment for both diseases. Diagnostic performance related to SARS-CoV-2 and Flu HGNC A/B detection was characterized for the BD SARS-CoV-2/ Flu HGNC for BD MAX System (MAX SARS-CoV-2/ Flu HGNC) multiplex assay in comparison with BD BioGx SARS-CoV-2 Reagents for BD MAX System ( BioGx SARS-CoV-2 MESHD) and the Cepheid Xpert(R) Xpress Flu HGNC/RSV (Xpert Flu HGNC). Two hundred and thirty-five nasopharyngeal specimens were obtained from external vendors. MAX SARS-CoV-2/ Flu HGNC had positive percent agreement (PPA) and negative percent agreement (NPA) values for SARS-CoV-2 and Flu HGNC A/B that met FDA-EUA acceptance criteria of >95%.

    Vaccine Rollout Strategies: The Case for Vaccinating Essential Workers Early

    Authors: Nicola Mulberry; Paul F Tupper; Christopher MacCabe; Erin Kirwin; Caroline Colijn

    doi:10.1101/2021.02.23.21252309 Date: 2021-02-25 Source: medRxiv

    In planning for upcoming mass vaccinations against COVID-19 MESHD, many jurisdictions have proposed using primarily age-based rollout strategies, where the oldest are vaccinated first and the youngest last. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection (and hence transmission of SARS-CoV-2), we propose that such age-based rollouts are both less equitable and less effective than strategies that prioritize essential workers. We demonstrate using modelling that strategies that target essential workers earlier consistently outperform those that do not, and that prioritizing essential workers provides a significant level of indirect protection for older adults. This conclusion holds across numerous outcomes, including cases, hospitalizations, deaths MESHD, prevalence of Long COVID, chronic impacts of COVID, quality adjusted life years lost and net monetary benefit lost. It also holds over a range of possible values for the efficacy of vaccination against infection. Our analysis focuses on regimes where the pandemic continues to be controlled with distancing and other measures as vaccination proceeds, and where the vaccination strategy is expected to last for over the coming 6-8 months - for example British Columbia, Canada. In such a setting with a total population of 5M, vaccinating essential workers sooner is expected to prevent over 200, 000 infections MESHD, over 600 deaths, and to produce a net monetary benefit of over $500M. 20-25% of the quality adjusted life years lost, and 28-34% of the net monetary benefit lost, are due to chronic impacts of COVID-19 MESHD.

    Visualization of SARS-CoV-2 Infection MESHD Scenes by 'Zero-Shot' Enhancements of Electron Microscopy Images

    Authors: Jakob Drefs; Sebastian Salwig; Jörg Lücke

    doi:10.1101/2021.02.25.432265 Date: 2021-02-25 Source: bioRxiv

    Electron microscopy (EM) recordings of infected tissues serve to diagnose a disease, and they can contribute to our understanding of infection processes. Consequently, a large number of EM images of the interaction of SARS-CoV-2 viruses with cells have been made available by numerous labs. However, due to EM recording techniques at high resolution, images of infection scenes are very noisy and they appear two dimensional ('flat'). Current research consequently aims (A) at methods that can remove noise, and (B) at techniques that allow for recovering a 3D impression of the virus or its parts. Here we discuss a novel method which can recover a spatial impression of a whole infection scene at high resolution. In contrast to previous approaches which aim at the reconstruction of single spike proteins PROTEIN or a single virus, the here used method can be applied to a single noisy EM image of an infection scene. As one example image, we show a high resolution image of SARS-CoV-2 viruses in Vero cell cultures (Fig. 1). The method we use is based on probabilistic machine learning algorithms which can operate in a 'zero-shot' setting, i.e., in a setting when just one noisy image (and no large and clean image corpus) is available. The probabilistic method we apply can estimate non-noisy images by inferring first order statistics (pixel means) across image patches using a previously learned probabilistic image representation. Estimating higher order statistics and appropriately chosen probabilistic models then allow for the generation of images that enhance details and give a spatial impression of a full nanoscopic scene.

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MeSH Disease
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SARS-CoV-2 Proteins


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