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Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management
Microbial Genomics ( IF 3.9 ) Pub Date : 2021-06-29 , DOI: 10.1099/mgen.0.000589
Andrew J Page 1 , Alison E Mather 1, 2 , Thanh Le-Viet 1 , Emma J Meader 3 , Nabil-Fareed Alikhan 1 , Gemma L Kay 1 , Leonardo de Oliveira Martins 1 , Alp Aydin 1 , David J Baker 1 , Alexander J Trotter 1, 2 , Steven Rudder 1 , Ana P Tedim 1, 4 , Anastasia Kolyva 1, 3 , Rachael Stanley 3 , Muhammad Yasir 1 , Maria Diaz 1 , Will Potter 3 , Claire Stuart 3 , Lizzie Meadows 1 , Andrew Bell 1 , Ana Victoria Gutierrez 1 , Nicholas M Thomson 1 , Evelien M Adriaenssens 1 , Tracey Swingler 2 , Rachel A J Gilroy 1 , Luke Griffith 2 , Dheeraj K Sethi 3 , Dinesh Aggarwal 5, 6, 7, 8 , Colin S Brown 5 , Rose K Davidson 2 , Robert A Kingsley 1, 2 , Luke Bedford 9 , Lindsay J Coupland 3 , Ian G Charles 1, 2 , Ngozi Elumogo 1, 3 , John Wain 1, 2 , Reenesh Prakash 3 , Mark A Webber 1, 2 , S J Louise Smith 10 , Meera Chand 5 , Samir Dervisevic 3 , Justin O'Grady 1, 2 , The Covid-Genomics Uk Cog-Uk Consortium
Affiliation  

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.

中文翻译:

对一个地区的 SARS-CoV-2 基因组进行大规模测序,可以进行详细的流行病学研究,并能够进行局部暴发管理

COVID-19 大流行已在世界范围内迅速蔓延。在英国,最初的高峰是在 2020 年 4 月;2020 年 3 月至 2020 年 8 月期间,在诺福克郡(英国)及周边地区,人口稳定、密度低,报告了 3200 多例病例。作为国家 COVID-19 基因组学联盟 (COG-UK) 活动的一部分) 我们对来自诺福克地区的阳性临床样本中的 SARS-CoV-2 基因组进行了全基因组测序。这些样本由诺福克及周边地区的四家主要医院、多家小型医院、护理机构和社区组织收集。我们将临床元数据与来自区域 SARS-CoV-2 基因组的测序数据相结合,以了解起源、遗传变异、病毒在该地区的传播和扩大(传播),并提供全国范围的背景信息。数据被反馈到国家大流行管理工作中,同时用于协助当地疫情分析。总体而言,评估了来自 1376 个病例的 1565 个阳性样本(每 10 万人中有 172 个);对于 140 个病例,有两到六个样本可提供纵向数据。这占该地区医院检测确定的所有阳性样本的 42.6%,包括有临床需要的人、卫生和护理人员及其家人。总共有 1035 个病例的基因组序列质量足以提供系统发育谱系。这些基因组属于 26 个不同的全球谱系,表明该地区有多个单独的介绍。此外,检测到 100 个基因上不同的英国血统,以每月约 2 个 SNP 的速度显示局部进化,并且随着大流行的进展,多个同时发生的血统。我们的分析:确定了与六个护理机构相关的离散子系;在纵向样本中没有发现再感染的证据;排除了院内暴发;确定了16个不在患者中的关键工人血统,表明感染控制措施是有效的;并发现与增加的传播性有关的 D614G 刺突蛋白突变在样本中占主导地位,并迅速证实了食品加工设施爆发病例的相关性。SARS-CoV-2阳性样本的大规模基因组测序为诺福克地区的公共卫生流行病学提供了宝贵的额外数据,
更新日期:2021-06-30
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