Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Pleotropic association between risk and prognosis of COVID-19 and gene expression in blood SERO and lung: A Mendelian randomization analysis

    Authors: Di Liu; Jingyun Yang; Bowen Feng; Wenjin Lu; Chuntao Zhao; Lizhuo Li; William Page; Ernest Guignon; Arturo Pilar; George N Gibson; - the Yale IMPACT Research Team; Charles S. Dela Cruz; Shelli F. Farhadian; Akiko Iwasaki; Albert I. Ko; Nathan D. Grubaugh; Anne L. Wyllie

    doi:10.1101/2020.09.02.20187179 Date: 2020-09-03 Source: medRxiv

    Background: Coronavirus disease 2019 (COVID-19) has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies ( GWAS MESHD) have identified potential genetic factors involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. Methods: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically/potentially causally associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. The GWAS summarized data for COVID-19 were provided by the COVID-19 Host Genetics Initiative and the Severe Covid-19 GWAS Group. Analyses were done for blood SERO and lung, respectively. Results: In blood SERO, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (beta [SE]=0.42 [0.09], P=4.75E06 and beta [SE]=-0.48 [0.11], P=6.76E06, respectively). Although no other probes were significant after correction for multiple testing in both blood SERO and lung, multiple genes as tagged by the top 5 probes were involved in inflammation MESHD or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood SERO blood MESHD coagulation. Conclusion: We identified IFNAR2 and other potential genes that could be involved in of the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism MESHD thromboembolism HP in COVID-19 and potential therapeutic target for effective treatment of COVID-19.

    Unravelling the modes of transmission TRANS of SARS-CoV-2 during a nursing home outbreak: looking beyond the church super-spread event

    Authors: Helene ACM Voeten; Reina S Sikkema; Marjolein Damen; Bas B Oude Munnink; Carla Arends; Ellen Stobberingh; Ellen Hoogervorst; Marion P.G. Koopmans; Ewout Fanoy

    doi:10.21203/rs.3.rs-63027/v1 Date: 2020-08-20 Source: ResearchSquare

    BackgroundAn outbreak of COVID-19 in a nursing home in the Netherlands, following an on-site church service held on March 8, 2020, triggered an investigation to unravel sources and chain(s) of transmission TRANS.MethodsEpidemiological data were collected from registries and through a questionnaire among church visitors. Symptomatic residents and healthcare workers (HCWs) were tested for SARS-CoV-2 by RT-PCR and subjected to whole genome sequencing ( WGS MESHD). Sequences from a selection of people from the same area were included as community reference.ResultsAfter the church service, 30 of 39 visitors (77%) developed symptoms; 14 were tested and were positive for COVID-19 (11 residents and 3 non-residents). In the following five weeks, 62 of 300 residents (21%) and 30 of 640 HCWs (5%) tested positive for COVID-19; 21 of 62 residents (34%) died. The outbreak was controlled through a cascade of measures. WGS of samples from residents and HCWs identified a diversity of sequence types, grouped into eight clusters. Seven resident church visitors all were infected with distinct viruses, four of which belonged to two larger clusters in the nursing home.ConclusionsAlthough initial investigation suggested the church service as source of the outbreak, detailed analysis showed a more complex picture, most consistent with widespread regional circulation of the virus in the weeks before the outbreak, and multiple introductions into the nursing home before the visitor ban. The findings underscore the importance of careful outbreak investigations to understand SARS-CoV-2 transmission TRANS to develop evidence-based mitigation measures.

    Analytical validity of nanopore sequencing for rapid SARS-CoV-2 genome analysis

    Authors: Rowena A Bull; Thiruni Adikari; Jillian M Hammond; Igor Stevanovski; James M Ferguson; Alicia G Beukers; Zin Naing; Malinna Yeang; Andrey Verich; Hasindu Gamaarachichi; Ki Wook Kim; Fabio Luciani Sr.; Sacha Stelzer-Braid; John-Sebastian Eden; William D Rawlinson; Sebastiaan J van Hal; Ira W Deveson

    doi:10.1101/2020.08.04.236893 Date: 2020-08-04 Source: bioRxiv

    Viral whole-genome sequencing ( WGS MESHD) provides critical insight into the transmission TRANS and evolution of Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2). Long-read sequencing devices from Oxford Nanopore Technologies (ONT) promise significant improvements in turnaround time, portability and cost, compared to established short-read sequencing platforms for viral WGS (e.g., Illumina). However, adoption of ONT sequencing for SARS-CoV-2 surveillance has been limited due to common concerns around sequencing accuracy. To address this, we performed viral WGS with ONT and Illumina platforms on 157 matched SARS-CoV-2-positive patient specimens and synthetic RNA controls, enabling rigorous evaluation of analytical performance SERO. Despite the elevated error rates observed in ONT sequencing reads, highly accurate consensus-level sequence determination was achieved, with single nucleotide variants (SNVs) detected at >99% sensitivity SERO and >98% precision above a minimum ~60-fold coverage depth, thereby ensuring suitability for SARS-CoV-2 genome analysis. ONT sequencing also identified a surprising diversity of structural variation within SARS-CoV-2 specimens that were supported by evidence from short-read sequencing on matched samples. However, ONT sequencing failed to accurately detect short indels and variants at low read-count frequencies. This systematic evaluation of analytical performance SERO for SARS-CoV-2 WGS MESHD will facilitate widespread adoption of ONT sequencing within local, national and international COVID-19 public health initiatives.

    Evaluation of NGS-based approaches for SARS-CoV-2 whole genome characterisation

    Authors: Caroline Charre; Christophe Ginevra; Marina Sabatier; Hadrien Regue; Solenne Brun; Gwendolyne Burfin; Caroline Scholtes; Florence Morfin; Martine Valette; Bruno Lina; Antonin Bal; Laurence Josset

    doi:10.1101/2020.07.14.201947 Date: 2020-07-15 Source: bioRxiv

    Since the beginning of the COVID-19 outbreak, SARS-CoV-2 whole-genome sequencing ( WGS MESHD) has been performed at unprecedented rate worldwide with the use of very diverse Next Generation Sequencing (NGS) methods. Herein, we compare the performance SERO of four NGS-based approaches for SARS-CoV-2 WGS MESHD. Twenty four clinical respiratory samples with a large scale of Ct values (from 10.7 to 33.9) were sequenced with four methods. Three used Illumina sequencing: an in-house metagenomic NGS (mNGS) protocol and two newly commercialized kits including a hybridization capture method developed by Illumina (DNA Prep with Enrichment kit and Respiratory Virus Oligo Panel MESHD, RVOP) and an amplicon sequencing method developed by Paragon Genomics (CleanPlex SARS-CoV-2 kit). We also evaluated the widely used amplicon sequencing protocol developed by ARTIC Network and combined with Oxford Nanopore Technologies (ONT) sequencing. All four methods yielded near-complete genomes (>99%) for high viral loads samples, with mNGS and RVOP producing the most complete genomes. For mid viral loads, 2/8 and 1/8 genomes were incomplete (<99%) with mNGS and both CleanPlex and RVOP, respectively. For low viral loads (Ct [≥]25), amplicon-based enrichment methods were the most sensitive techniques yielding complete genomes for 7/8 samples. All methods were highly concordant in terms of identity in complete consensus sequence. Just one mismatch in two samples was observed in CleanPlex vs the other methods, due to the dedicated bioinformatics pipeline setting a high threshold to call SNP compared to reference sequence. Importantly, all methods correctly identified a newly observed 34-nt deletion in ORF6 but required specific bioinformatic validation for RVOP. Finally, as a major warning for targeted techniques, a default of coverage in any given region of the genome should alert to a potential rearrangement or a SNP in primer annealing or probe-hybridizing regions and would require regular updates of the technique according to SARS-CoV-2 evolution.

    WHOLE-GENOME SEQUENCING AND DE NOVO ASSEMBLY OF A 2019 NOVEL CORONAVIRUS (SARS-COV-2) STRAIN ISOLATED IN VIETNAM

    Authors: Lam Tung Le; Hieu Trung Nguyen; Trang Hong Nguyen; Thuong Thi Ho; Linh Huyen Tran; Tien Thuy Luu; Thao Thi Ngoc Nguyen; Loan Thi Kim Huynh; Quang Duy Pham; Quang Chan Luong; Thang Minh Cao; Thuong Vu Nguyen; Ha Hoang; Hoang Ha Chu; Lan Trong Phan; Hai Nam Truong

    doi:10.1101/2020.06.12.149377 Date: 2020-06-13 Source: bioRxiv

    The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing ( WGS MESHD) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence and de novo assemble the whole genome of SARS-CoV-2 using PacBios SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed and de novo assembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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