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Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study - 22/10/20

Doi : 10.1016/S1473-3099(20)30562-4 
Luke W Meredith, PhD a, , , William L Hamilton, PhD b, c, , , Ben Warne, MB Bchir b, c, Charlotte J Houldcroft, PhD b, Myra Hosmillo, PhD a, Aminu S Jahun, PhD a, Martin D Curran, PhD d, Surendra Parmar, PhD d, Laura G Caller, PhD a, e, Sarah L Caddy, PhD b, f, Fahad A Khokhar, BSc b, f, Anna Yakovleva, BSc a, Grant Hall, BS a, Theresa Feltwell b, Sally Forrest, BSc b, f, Sushmita Sridhar, BS b, f, g, Michael P Weekes, PhD b, f, Stephen Baker, ProfPhD b, f, Nicholas Brown, MD d, Elinor Moore, MBBS c, Ashley Popay, BSc h, Iain Roddick, BSc h, Mark Reacher, MD h, Theodore Gouliouris, PhD c, d, Sharon J Peacock, ProfFRCP b, i, Gordon Dougan, ProfPhD b, f, M Estée Török, FRCP b, c, , , Ian Goodfellow, ProfPhD a, , ,
a Department of Pathology, University of Cambridge, Cambridge, UK 
b Department of Medicine, University of Cambridge, Cambridge, UK 
c Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK 
d Public Health England Clinical Microbiology and Public Health Laboratory, Cambridge, UK 
e Francis Crick Institute, London, UK 
f Cambridge Institute for Therapeutic Immunology and Infectious Disease, Cambridge, UK 
g Wellcome Sanger Institute, Hinxton, UK 
h Field Epidemiology, Field Service, National Infection Service, Public Health England, Cambridge, UK 
i National Infection Service, Public Health England, London, UK 

* Correspondence to: Dr M Estée Török, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK Department of Medicine University of Cambridge Cambridge CB2 0QQ UK ** Prof Ian Goodfellow, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK Department of Pathology University of Cambridge Cambridge CB2 0QQ UK

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Summary

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 (supported by UK Research and Innovation, the National Institute of Health Research, the Wellcome Sanger Institute), the Wellcome Trust, the Academy of Medical Sciences and the Health Foundation, and the National Institute for Health Research Cambridge Biomedical Research Centre.

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© 2020  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 20 - N° 11

P. 1263-1271 - novembre 2020 Retour au numéro
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