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

Luke W. Meredith, William L. Hamilton, Ben Warne, Charlotte J. Houldcroft, Myra Hosmillo, Aminu S. Jahun, Martin Curran, Surendra Parmar, Laura G. Caller, Sarah L. Caddy, Fahad A. Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Sally Forrest, Sushmita Sridhar, Michael P. Weekes, Stephen Baker, Nicholas Brown, Elinor MooreAshley Popay, Iain Roddick, Mark Reacher, Theodore Gouliouris, Sharon Peacock, Gordon Dougan, M. Estée Török*, Ian Goodfellow

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)1263-1272
Number of pages10
JournalThe Lancet Infectious Diseases
Volume20
Issue number11
Early online date14 Jul 2020
DOIs
Publication statusPublished - 11 Feb 2021

Bibliographical note

Funding Information: This work was funded by COVID-19 Genomics UK, which is supported by funding from the Medical Research Council part of UK Research and Innovation, the National Institute of Health Research, and Genome Research, 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 CUH (BW, GD, MET). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute of Health Research, or the Department of Health and Social Care.
CJH, SLC, MPW, and SB report grants from Wellcome. GH reports grants from Rotary International. MET reports grants from Academy of Medical Sciences, Health Foundation, grants from Medical Research Council, grants and non-financial support from National Institute of Health Research, during the conduct of the study. MET has published books with Oxford University Press and receives royalty payments from them, personal fees from the Wellcome Sanger Institute, personal fees from University of Cambridge, outside the submitted work. IG reports grants from Wellcome; and grants from Medical Research Council part of UK Research & Innovation. All other authors declare no competing interests.

Open Access: This is an Open Access article under the CC BY 4.0 license.

Publisher Copyright: © 2020 The Author(s). Published by Elsevier Ltd

Citation: Luke W Meredith, William L Hamilton, Ben Warne, Charlotte J Houldcroft, Myra Hosmillo, Aminu S Jahun, Martin D Curran, Surendra Parmar, Laura G Caller, Sarah L Caddy, Fahad A Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Sally Forrest, Sushmita Sridhar, Michael P Weekes, Stephen Baker, Nicholas Brown, Elinor Moore, Ashley Popay, Iain Roddick, Mark Reacher, Theodore Gouliouris, Sharon J Peacock, Gordon Dougan, M Estée Török, Ian Goodfellow, Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study, The Lancet Infectious Diseases, Volume 20, Issue 11, 2020, Pages 1263-1271, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(20)30562-4.

DOI: https://doi.org/10.1016/S1473-3099(20)30562-4

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