Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.

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Meredith, Luke W 
Hamilton, William L 
Houldcroft, Charlotte J 

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.

Adolescent, Adult, Aged, Aged, 80 and over, Betacoronavirus, COVID-19, Child, Child, Preschool, Coronavirus Infections, Cross Infection, England, Female, Genome, Viral, Hospitals, University, Humans, Infant, Infant, Newborn, Infection Control, Male, Middle Aged, Pandemics, Patient Safety, Phylogeny, Pneumonia, Viral, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Prospective Studies, SARS-CoV-2, Whole Genome Sequencing, Young Adult
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Lancet Infect Dis
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Elsevier BV
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Wellcome Trust (206298/B/17/Z)
Wellcome Trust (207498/Z/17/Z)
Wellcome Trust (207498/Z/17/Z)
Wellcome Trust (108070/Z/15/Z)
MRC (MC_PC_19027)
Medical Research Council (MC_PC_19027)
Medical Research Council (MR/N029399/1)
Wellcome Trust (215515/Z/19/Z)
This work was funded COG-UK, which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. It was also supported by the Wellcome (Senior Fellowship 207498/Z/17/Z and ARTIC Network Collaborative Award 206298/B/17/Z to IG, Collaborative Award 204870/Z/16/Z supporting CJH, Senior Research Fellowship to SGB 215515/Z/19/Z, Senior Clinical Research Fellowship 108070/Z/15/Z to MPW), the Academy of Medical Sciences and the Health Foundation (Clinician Scientist Fellowship to MET), and the National Institute for Health Research Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust (BW, GD, MET). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.