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

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

doi:10.1016/s1473-3099(20)30562-4

Abstract

BackgroundThe 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.MethodsIn 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.FindingsBetween 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.InterpretationWe 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.FundingCOVID-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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population in December, 2019,1 originating from an intermediate animal host.[2]
On a larger population scale, genomic surveillance of SARS-CoV-2 can inform which lineages of the virus are circulating in the human population, how these change over time as an indicator of the success of control measures, how often new sources of virus are introduced from other geographical areas, and how the virus evolves in response to interventions
Added value of this study We present the first report, to our knowledge, applying rapid genome sequencing to systematically investigate SARS-CoV-2 health-care associated infections, integrating genomic and epidemiological data to identify transmission networks and inform targeted infection control interventions

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population in December, 2019,1 originating from an intermediate animal host.[2] Owing to the error prone nature of the viral replication process, RNA viruses, such as SARS-CoV-2, accumulate mutations over time resulting in sequence diversity. The current mutation rate of SARS-CoV-2 is estimated to be approximately 2·5 nucleotides per month.[3] Sequencing of SARS-CoV-2 can provide valuable information on virus biology, transmission, and popu lation dynamics.[4,5,6,7] When linked with detailed epide miological data and on a timescale of days, genomic data can support epidemiological investigations of potential hospital-acquired infections. On a larger population scale, genomic surveillance of SARS-CoV-2 can inform which lineages of the virus are circulating in the human population, how these change over time as an indicator of the success of control measures, how often new sources of virus are introduced from other geographical areas, and how the virus evolves in response to interventions

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