Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (1389)

Fever (829)

Cough (689)

Hypertension (489)

Anxiety (486)


age categories (3897)

Transmission (3404)

gender (1792)

fomite (1391)

contact tracing (1267)

    displaying 31 - 40 records in total 18267
    records per page

    Structural basis for the inhibition of the SARS-CoV-2 RNA-dependent RNA polymerase by favipiravir-RTP

    Authors: Katerina Naydenova; Kyle W Muir; Long-Fei Wu; Ziguo Zhang; Francesca Coscia; Mathew J Peet; Pablo Castro-Hartmann; Pu Qian; Kasim Sader; Kyle Dent; Dari Kimanius; John D Sutherland; Jan Lowe; David Barford; Christopher J Russo; Makoto Sakaguchi; Hideki Tomioka; Munehisa Shimamura; Sachiko Okamoto; Yasunori Amaishi; Hideto Chono; Junichi Mineno; Takao Komatsuno; Yoshimi Saito; Hiromi Rakugi; Ryuichi Morishita; Hironori Nakagami; Jacob Moran-Gilad; Yakir Berchenko; Itay Bar-Or; Ariel Kushmaro; Timothy Spector; Claire J Steves

    doi:10.1101/2020.10.21.347690 Date: 2020-10-21 Source: bioRxiv

    The RNA polymerase inhibitor, favipiravir, is currently in clinical trials as a treatment for infection MESHD with SARS-CoV-2, despite limited information about the molecular basis for its activity. Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 Ang. The structure shows clear evidence for the inhibitor at the catalytic site of the enzyme, and resolves the conformation of key side chains and ions surrounding the binding pocket. Polymerase activity assays indicate that the inhibitor is weakly incorporated into the RNA primer strand, and suppresses RNA replication in the presence of natural nucleotides. The structure reveals an unusual, non-productive binding mode of favipiravir-RTP at the catalytic site of SARS-CoV2 RdRp which explains its low rate of incorporation into the RNA primer strand. Together, these findings inform current and future efforts to develop polymerase inhibitors for SARS coronaviruses.

    Restriction of SARS-CoV-2 Replication by Targeting Programmed -1 Ribosomal Frameshifting In Vitro

    Authors: Yu Sun; Laura Abriola; Yulia V. Surovtseva; Brett D. Lindenbach; Junjie U. Guo

    doi:10.1101/2020.10.21.349225 Date: 2020-10-21 Source: bioRxiv

    Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) requires programmed -1 ribosomal frameshifting (-1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in -1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a -1 PRF inhibitor of SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on -1 PRF of other beta coronaviruses. Importantly, frameshift inhibition by merafloxacin substantially impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing the proof of principle of targeting -1 PRF as an effective antiviral strategy for SARS-CoV-2.

    A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

    Authors: Vincent Dubee; Pierre-Marie Roy; Bruno Vielle; Elsa Parot-Schinkel; Odile Blanchet; Astrid Darsonval; Caroline Lefeuvre; Chadi Abbara; Sophie Boucher; Edouard Devaud; Olivier Robineau; Patrick Rispal; Thomas Guimard; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.19.20214940 Date: 2020-10-21 Source: medRxiv

    Background The efficacy of hydroxychloroquine in coronavirus disease MESHD 2019 (COVID-19) remains controversial. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age TRANS 75 years or more, age TRANS between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (3 L/min or more). Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on Day 0 followed by 400 mg per day for 8 days or a placebo. The primary endpoint was a composite of death MESHD or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10. Results The trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age TRANS was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45-2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints. Conclusion In this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

    Low-Cost Manually Assembled Open Source Reader for Isothermal Pathogen Detection from Saliva using RT-LAMP: SARS-CoV-2 Use Case

    Authors: John C Bramley; Jason E Waligorski; Colin L Kremitzki; Mariel J Liebeskind; Alex Yenkin; Xinyuan E Xu; Matthew A Lalli; Jane A O'Halloran; Philip A Mudd; Stacey House; Robi Mitra; Jeffrey D Milbrandt; William J Buchser; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.19.20215319 Date: 2020-10-21 Source: medRxiv

    Distributed 'Point-of-Care' or 'at-Home' testing is an important component for a complete suite of testing solutions. This manuscript describes the construction and operation of a platform technology designed to meet this need. The ongoing COVID-19 pandemic will be used as the proof-of-concept for the efficacy and deployment of this platform. The technology outlined consists of a one-pot, reverse-transcription loop-mediated isothermal amplification (RT-LAMP) chemistry coupled with a low-cost and user-assembled reader using saliva as input. This platform is readily adapted to a wide range of pathogens due to the genetic basis of the reaction. A complete guide to the construction of the reader as well as the production of the reaction chemistry are provided here. Additionally, analytical limit of detection data and the results from saliva testing of SARS-CoV-2, are presented. The platform technology outlined here demonstrates a rapid, distributed, molecular point-of-care solution for pathogen detection using crude sample input.

    Accuracy of Healthcare Professionals Nasopharyngeal Swab Technique in SARS-CoV-2 Specimen Collection

    Authors: Robbie Woods; Michael Walsh; Kellie Nwaokorie; Jana Crowley; Peter Lacy; Eoghan de Barra; Matthew A Lalli; Jane A O'Halloran; Philip A Mudd; Stacey House; Robi Mitra; Jeffrey D Milbrandt; William J Buchser; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.19.20213140 Date: 2020-10-21 Source: medRxiv

    Background: The COVID-19 pandemic has caused huge pressure on healthcare systems worldwide. Public health measures to control the virus are reliant on testing, including appropriate collection of specimens for analysis. Methods: A prospective study of nasopharyngeal swab technique by staff in an academic tertiary referral centre was carried out. Nasopharyngeal swab technique was evaluated by a novel design of a navigated swab on a three-dimensional model head. Results: Swab technique of 228 participants was assessed. Technique was poor, with a success rate of nasopharyngeal swabbing at 38.6%. Angle and length of insertion were significantly different between those with successful and unsuccessful technique. Doctors were significantly more accurate than nurses and non-healthcare professionals (p<0.01). Conclusion: Inaccurate specimen collection from poor swab technique could contribute to false negative rate of testing for SARS-CoV-2. Specific training in nasopharyngeal anatomy and swab technique may improve the accuracy of nasopharyngeal swabbing.

    Percentage HScore confirms low incidence of secondary haemophagocytic lymphohistiocytosis MESHD in hospitalised COVID-19 patients

    Authors: Michael R Ardern-Jones; Matthew Stammers; Hang T.T. Phan; Florina Borca; Anastasia Koutalopoulou; Ying Teo; James Batchelor; Trevor Smith; Andrew Duncombe; Stacey House; Robi Mitra; Jeffrey D Milbrandt; William J Buchser; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.19.20214015 Date: 2020-10-21 Source: medRxiv

    Objective: It has been assumed that a significant proportion of COVID-19 patients show evidence of hyperinflammation of which secondary haemophagocytic lymphohistiocytosis MESHD (sHLH) is the most severe manifestation. To facilitate diagnosis of sHLH the HScore has been developed and validated. We set out to examine the prevalence SERO of sHLH-like hyperinflammation in COVID-19. Methods: We retrospectively examined HScore parameters in 626 COVID-19 cases admitted to our institute of which 567 were suitable for analysis and compared these to a cohort of confirmed infection TRANS infection MESHD associated sHLH cases. To account for missing data, we calculated the maximum possible HScore of the recorded parameters (%HScore). Results: Early measurement of HScore parameters (day -1 to 4 from diagnosis) strongly predicted the %HScore over the course of the admission (p <0.0001). The retrospective cohort of sHLH showed significantly higher %HScores as compared to COVID-19 (median 73.47 vs 18.13 respectively, p <0.0001). The overall prevalence SERO of individuals with an 80% probability of sHLH in our COVID-19 cohort was 1.59% on admission and only rose to 4.05% during the whole disease course. In the small cohort with scores suggestive of sHLH, there was no excess mortality compared with the whole cohort. %HScores were higher in younger patients (p<0.0001) and did not reliably predict outcome at any cut-off value (AUROC 0.533, p=0.211; OR 0.99). Conclusion: Surprisingly, these findings show that sHLH-type hyperinflammation is not prevalent in COVID-19, and %HScores do not predict outcome. Therefore, new algorithms are required to optimise case selection for clinical trials of targeted anti-inflammatory interventions.

    SI epidemic model applied to COVID-19 data in mainland China

    Authors: Jacques Demongeot; Quentin Griette; pierre magal; Florina Borca; Anastasia Koutalopoulou; Ying Teo; James Batchelor; Trevor Smith; Andrew Duncombe; Stacey House; Robi Mitra; Jeffrey D Milbrandt; William J Buchser; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.19.20214528 Date: 2020-10-21 Source: medRxiv

    The article is devoted the parameters identification in the SI model. We consider several method, starting from Liu et al. [17] to fit the early cumulative data of Sars-CoV2 in mainland China. This method provides a way to compute the parameters at the early stage of the epidemic. Next, we establish an identifiability result in the spirit of Hadeler [19]. Then we use the Bernoulli-Verhulst model as a phenomenological model to fit the data and derive some result on the parameters identification. The last part of the paper is devoted to some numerical Algorithms to fit a daily piecewise constant rate of transmission TRANS.

    Extending the range of COVID-19 risk factors ina Bayesian network model for personalised riskassessment

    Authors: Georgina Prodhan; Quentin Griette; pierre magal; Florina Borca; Anastasia Koutalopoulou; Ying Teo; James Batchelor; Trevor Smith; Andrew Duncombe; Stacey House; Robi Mitra; Jeffrey D Milbrandt; William J Buchser; Emma D'Anglejan; Sylvain Diamantis; Marc-Antoine Custaud; Isabelle Pellier; Alain Mercat

    doi:10.1101/2020.10.20.20215814 Date: 2020-10-21 Source: medRxiv

    A need is emerging for individuals to gauge their own risks of coronavirus infection MESHD as it becomes apparent that contact tracing TRANS to contain the spread of the virus is not working in many societies. This paper presents an extension of an existing Bayesian network model for an application in which people can add their own personal risk factors to calculate their probability of exposure to the virus and likely severity if they do catch the illness. The data need not be shared with any central authority. In this way, people can become more aware of their individual risks and adjust their behaviour accordingly, as many countries prepare for a second wave of infections MESHD or a prolonged pandemic. This has the advantage not only of preserving privacy but also of containing the virus more effectively by allowing users to act without the time lag of waiting to be informed that a contact has been tested and confirmed COVID-19 positive. Through a nuanced assessment of individual risk, it could also release many people from isolation who are judged highly vulnerable using cruder measures, helping to boost economic activity and decrease social isolation without unduly increasing transmission risk TRANS. Although much has been written and reported about single risk factors, little has been done to bring these factors together in a user-friendly way to give an overall risk rating. The causal probabilistic model presented here shows the power of Bayesian networks to represent the interplay of multiple, dependent variables and to predict outcomes. The network, designed for use in the UK, is built using detailed data from government and health authorities and the latest research, and is capable of dynamic updates as new information becomes available. The focus of the paper is on the extended set of risk factors.

    Efficacy of stay-at-home policy and transmission TRANS of COVID-19 in Toronto, Canada: a mathematical modeling study

    Authors: Pei Yuan; Juan Li; Elena Aruffo; Qi Li; Tingting Zheng; Nicholas Ogden; Beate Sander; Jane Heffernan; Evgenia Gatov; Effie Gournis; Sarah Collier; Yi Tan; Jun Li; Julien Arino; Jacques Belair; James Watmough; Jude Dzevela Kong; Iain Moyles; Huaiping Zhu

    doi:10.1101/2020.10.19.20181057 Date: 2020-10-21 Source: medRxiv

    Background In many parts of the world, restrictive non-pharmaceutical interventions (NPI) that aim to reduce contact rates, including stay-at-home orders, limitations on gatherings, and closure of public places, are being lifted, with the possibility that the epidemic resurges if alternative measures are not strong enough. Here we aim to capture the combination of use of NPIs and reopening measures which will prevent an infection rebound. Methods We employ a SEAIR model with a household structure able to capture the stay-at-home policy (SAHP). To reflect the changes in the SAHP over the course of the epidemic, we vary the SAHP compliance rate, assuming that the time to compliance of all the people requested to stay-at-home follows a Gamma distribution. Using confirmed case TRANS data for the City of Toronto, we evaluate basic and instantaneous reproduction numbers TRANS and simulate how the average household size, the stay-at-home rate, the efficiency and duration of SAHP implementation, affect the outbreak trajectory. Findings The estimated basic reproduction number TRANS R_0 TRANS was 2.36 (95% CI: 2.28, 2.45) in Toronto. After the implementation of the SAHP, the contact rate outside the household fell HP by 39%. When people properly respect the SAHP, the outbreak can be quickly controlled, but extending its duration beyond two months (65 days) had little effect. Our findings also suggest that to avoid a large rebound of the epidemic, the average number of contacts per person per day should be kept below nine. This study suggests that fully reopening schools, offices, and other activities, is possible if the use of other NPIs is strictly adhered to. Interpretation Our model confirmed that the SAHP implemented in Toronto had a great impact in controlling the spread of COVID-19. Given the lifting of restrictive NPIs, we estimated the thresholds values of the maximum number of contacts, probability of transmission TRANS and testing needed to ensure that the reopening will be safe, i.e. maintaining an R_t<1.

    From multiplex serology to serolomics: A novel approach to the antibody SERO response against the SARS-CoV-2 proteome

    Authors: Julia Butt; Rajagopal Murugan; Theresa Hippchen; Sylvia Olberg; Monique van Straaten; Hedda Wardemann; Erec Stebbins; Hans-Georg Kraeusslich; Ralf Bartenschlager; Hermann Brenner; Vibor Laketa; Ben Schoettker; Barbara Mueller; Uta Merle; Tim Waterboer; James Watmough; Jude Dzevela Kong; Iain Moyles; Huaiping Zhu

    doi:10.1101/2020.10.19.20214916 Date: 2020-10-21 Source: medRxiv

    Background: The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays SERO to assess SARS-CoV-2 epidemiology. We therefore aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody SERO responses to the SARS-CoV-2 proteome. Methods: Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance SERO was assessed in a Covid-19 case cohort (n=48 hospitalized patients from Heidelberg) as well as n=85 age TRANS- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial Enzyme-linked immunosorbent ( ELISA) assays SERO. Results: A sensitivity SERO of 100% (95% CI: 86%-100%) was achieved in Covid-19 patients 14 days post symptom onset TRANS with dual sero-positivity to SARS-CoV-2 N MESHD and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96%-100%). Antibody SERO responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N MESHD. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody SERO response. Conclusion: This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity SERO and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero- prevalence SERO.

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MeSH Disease
Human Phenotype

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