快速实施 SARS-CoV-2 测序以调查与医疗保健相关的 COVID-19 病例：一项前瞻性基因组监测研究。
Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.
机构信息
Department of Pathology, University of Cambridge, Cambridge, UK.
Department of Medicine, University of Cambridge, Cambridge, UK; Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
出版信息
Lancet Infect Dis. 2020 Nov;20(11):1263-1272. doi: 10.1016/S1473-3099(20)30562-4. Epub 2020 Jul 14.
BACKGROUND
The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.
METHODS
In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases.
FINDINGS
Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting.
INTERPRETATION
We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings.
FUNDING
COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.
背景
目前尚不清楚与医疗保健相关的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的负担和影响。我们旨在通过研究快速 SARS-CoV-2 测序与详细的流行病学分析结合使用，来调查与医疗保健相关的 SARS-CoV-2 感染并为感染控制措施提供信息。
方法
在这项前瞻性监测研究中，我们在英国剑桥的医院以及英格兰东部的随机医院中建立了快速 SARS-CoV-2 纳米孔测序，从聚合酶链反应（PCR）阳性的诊断样本中采集样本，可在不到 24 小时内实现样本到测序。我们建立了每周审查和报告系统，将基因组和流行病学数据相结合，以调查疑似与医疗保健相关的 COVID-19 病例。
结果
2020 年 3 月 13 日至 4 月 24 日期间，我们从英格兰东部的 5613 名 COVID-19 患者中收集了临床数据和样本。我们对 1000 个样本进行了测序，得到了 747 个高质量的基因组。我们结合了来自我们医院的 299 名患者的流行病学和基因组分析，并确定了涉及 159 名患者的 35 个相同病毒簇。92 名（58%）患者具有强烈的流行病学联系，32 名（20%）患者具有合理的流行病学联系。这些结果反馈给临床、感染控制和医院管理团队，导致感染控制干预措施的实施，并为患者安全报告提供了信息。
结论
我们在英国的一家医院建立了实时 SARS-CoV-2 基因组监测，并展示了基因组和流行病学分析相结合对调查与医疗保健相关的 COVID-19 的益处。这种方法使我们能够检测到隐匿性传播事件，并确定有机会将感染控制干预措施作为进一步减少与医疗保健相关感染的目标。我们的发现对国家公共卫生政策具有重要意义，因为它们能够快速跟踪和调查医院和社区环境中的感染。
资金
COVID-19 Genomics UK 由英国卫生部、英国研究与创新署和惠康桑格研究所共同资助。
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