Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: multicenter, prospective study

  1. Oliver Stirrup
  2. James Blackstone
  3. Fiona Mapp
  4. Alyson MacNeil
  5. Monica Panca
  6. Alison Holmes
  7. Nicholas Machin
  8. Gee Yen Shin
  9. Tabitha Mahungu
  10. Kordo Saeed
  11. Tranprit Saluja
  12. Yusri Taha
  13. Nikunj Mahida
  14. Cassie Pope
  15. Anu Chawla
  16. Maria-Teresa Cutino-Moguel
  17. Asif Tamuri
  18. Rachel Williams
  19. Alistair Darby
  20. David L Robertson
  21. Flavia Flaviani
  22. Eleni Nastouli
  23. Samuel Robson
  24. Darren Smith
  25. Kenneth Laing
  26. Irene Monahan
  27. Beatrix Kele
  28. Sam Haldenby
  29. Ryan George
  30. Matthew Bashton
  31. Adam A Witney
  32. Matthew Byott
  33. Francesc Coll
  34. Michael Chapman
  35. Sharon J Peacock
  36. COG‐UK HOCI Investigators
  37. The COVID‐19 Genomics UK (COG‐UK) Consortium
  38. Joseph Hughes
  39. Gaia Nebbia
  40. David G Partridge
  41. Matthew Parker
  42. James Richard Price
  43. Christine Peters
  44. Sunando Roy
  45. Luke B Snell
  46. Thushan I de Silva
  47. Emma Thomson
  48. Paul Flowers
  49. Andrew Copas
  50. Judith Breuer  Is a corresponding author
  1. University College London, United Kingdom
  2. Imperial College Healthcare NHS Trust, United Kingdom
  3. Manchester University NHS Foundation Trust, United Kingdom
  4. University College London Hospitals NHS Foundation Trust, United Kingdom
  5. Royal Free London NHS Foundation Trust, United Kingdom
  6. University Hospital Southampton NHS Foundation Trust, United Kingdom
  7. Sandwell & West Birmingham Hospitals NHS Trust, United Kingdom
  8. Newcastle-upon-Tyne Hospitals NHS Foundation Trust, United Kingdom
  9. Nottingham University Hospitals NHS Trust, United Kingdom
  10. St George's University Hospitals NHS Foundation Trust, United Kingdom
  11. Liverpool University Hospitals NHS Foundation Trust, United Kingdom
  12. Barts Health NHS Trust, United Kingdom
  13. University of Liverpool, United Kingdom
  14. University of Glasgow, United Kingdom
  15. Guy's and St Thomas' Hospital NHS Foundation Trust, United Kingdom
  16. University of Portsmouth, United Kingdom
  17. Northumbria University, United Kingdom
  18. St George's, University of London, United Kingdom
  19. London School of Hygiene & Tropical Medicine, United Kingdom
  20. Health Data Research UK, United Kingdom
  21. University of Cambridge, United Kingdom
  22. Guy's and St Thomas' NHS Foundation Trust, United Kingdom
  23. Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom
  24. University of Sheffield, United Kingdom
  25. NHS Greater Glasgow and Clyde, United Kingdom
  26. University of Strathclyde, United Kingdom

Abstract

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected ≥48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated.

Results: A total of 2170 HOCI cases were recorded from October 2020-April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95%CI 0.85-3.01; P=0.14) or rapid (0.85, 0.48-1.50; P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.

Conclusion: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) [grant code: MC_PC_19027], and Genome Research Limited, operating as the Wellcome Sanger Institute.

Clinical trial number: ClinicalTrials.gov Identifier: NCT04405934.

Data availability

A fully anonymised version of the dataset generated and analysed for this study is available on the UCL Research Data Repository (https://doi.org/10.5522/04/20769637.v1).

The following data sets were generated

Article and author information

Author details

  1. Oliver Stirrup

    Institute for Global Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8705-3281
  2. James Blackstone

    The Comprehensive Clinical Trials Unit, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4335-5269
  3. Fiona Mapp

    Institute for Global Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Alyson MacNeil

    Comprehensive Clinical Trials Unit, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8409-2755
  5. Monica Panca

    Comprehensive Clinical Trials Unit, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  6. Alison Holmes

    Imperial College Healthcare NHS Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Nicholas Machin

    Manchester University NHS Foundation Trust, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  8. Gee Yen Shin

    University College London Hospitals NHS Foundation Trust, London, United Kingdom
    Competing interests
    Gee Yen Shin, has an unpaid role as Deputy Chair, British Medical Association London Regional Council. The author has no other competing interests to declare..
  9. Tabitha Mahungu

    Royal Free London NHS Foundation Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  10. Kordo Saeed

    University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
    Competing interests
    No competing interests declared.
  11. Tranprit Saluja

    Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  12. Yusri Taha

    Department of Virology and Infectious Diseases, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom
    Competing interests
    No competing interests declared.
  13. Nikunj Mahida

    Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
    Competing interests
    No competing interests declared.
  14. Cassie Pope

    St George's University Hospitals NHS Foundation Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  15. Anu Chawla

    Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
    Competing interests
    No competing interests declared.
  16. Maria-Teresa Cutino-Moguel

    Barts Health NHS Trust, London, United Kingdom
    Competing interests
    Maria-Teresa Cutino-Moguel, received payment for anonymous interview conducted by Adkins Research Group. The author has no other competing interests to declare..
  17. Asif Tamuri

    Research Computing, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  18. Rachel Williams

    Department of Genetics and Genomic Medicine, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  19. Alistair Darby

    Centre for Genomic Research, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    No competing interests declared.
  20. David L Robertson

    MRC-University of Glasgow Centre For Virus Research, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6338-0221
  21. Flavia Flaviani

    Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4210-0451
  22. Eleni Nastouli

    University College London Hospitals NHS Foundation Trust, London, United Kingdom
    Competing interests
    Eleni Nastouli, holds grants by NIHR, EPSRC, MRC-UKRI , H2020, ViiV Healthcare, Pfizer and Amfar, and has received grants to attend meetings from H2020 and ViiV Healthcare..
  23. Samuel Robson

    Centre for Enzyme Innovation, University of Portsmouth, Portsmouth, United Kingdom
    Competing interests
    No competing interests declared.
  24. Darren Smith

    Department of Applied Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom
    Competing interests
    Darren Smith, holds the following grants that are not specifically for the present work: COG-UK, PHE test and trace funded the sequencing aspect. HOCI funded a technician to support sequencing during study period. The author has no other competing interests to declare."105556".
  25. Kenneth Laing

    Institute for Infection and Immunity, St George's, University of London, London, United Kingdom
    Competing interests
    No competing interests declared.
  26. Irene Monahan

    Institute for Infection and Immunity, St George's, University of London, London, United Kingdom
    Competing interests
    No competing interests declared.
  27. Beatrix Kele

    Barts Health NHS Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  28. Sam Haldenby

    Centre for Genomic Research, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    No competing interests declared.
  29. Ryan George

    Manchester University NHS Foundation Trust, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  30. Matthew Bashton

    Department of Applied Sciences, Northumbria University, Newcastle-upon-Tyne, United Kingdom
    Competing interests
    No competing interests declared.
  31. Adam A Witney

    Institute for Infection and Immunity, St George's, University of London, London, United Kingdom
    Competing interests
    No competing interests declared.
  32. Matthew Byott

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  33. Francesc Coll

    Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, United Kingdom
    Competing interests
    Francesc Coll, received consulting fees from Next Gen Diagnostics LLC (during 2018/2019), received payment or honoria for lectures from University of Cambridge and Wellcome Genome Campus Advanced Courses, and received support for attending meeting and/or travel to meetings from European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), The American Society for Microbiology (ASM), Microbiology Society, European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), and the British Infection Association (BIA). The author has no other competing interests to declare..
  34. Michael Chapman

    Health Data Research UK, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  35. Sharon J Peacock

    Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    Sharon J Peacock, received consultancy fees from Pfizer (Coronavirus External Advisory Board) and Melinta Therapeutics, received payment from SVB Leerink for a round table meeting and for Mary Strauss Distinguished Public Lecture from the Fralin Biomedical Research Institute, US, and support for attending ICPIC conference, Geneva and World Health Summit, Berlin in 2021, and hold stocks or stock options in Specific Technologies (European Union Scientific Advisory Board) and Next Gen Diagnostics (Scientific Advisory Board). SP also serves as Chair, Medical Advisory Committee, Sir Jules Thorn Charitable Trust, Board member of the Wellcome SEDRIC (Surveillance and Epidemiology of Drug Resistant Consortium), and Non-Executive Director of Cambridge University Hospitals NHS Foundation Trust. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1718-2782
  36. COG‐UK HOCI Investigators

  37. The COVID‐19 Genomics UK (COG‐UK) Consortium

  38. Joseph Hughes

    MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  39. Gaia Nebbia

    Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  40. David G Partridge

    Directorate of Laboratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0417-2016
  41. Matthew Parker

    Sheffield Bioinformatics Core, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    No competing interests declared.
  42. James Richard Price

    Imperial College Healthcare NHS Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  43. Christine Peters

    NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  44. Sunando Roy

    Division of Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  45. Luke B Snell

    Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
    Competing interests
    No competing interests declared.
  46. Thushan I de Silva

    Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    No competing interests declared.
  47. Emma Thomson

    MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  48. Paul Flowers

    School of Psychological Sciences and Health, University of Strathclyde, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  49. Andrew Copas

    Institute for Global Health, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  50. Judith Breuer

    Division of Infection and Immunity, University College London, London, United Kingdom
    For correspondence
    j.breuer@ucl.ac.uk
    Competing interests
    Judith Breuer, is a member of the SAGE hospital onset covid working group 2020-2022. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8246-0534

Funding

Medical Research Council

  • Judith Breuer

National Institute for Health and Care Research (MC_PC_19027)

  • Judith Breuer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval for the study was granted by NHS HRA (REC 20/EE/0118). The need for consent from individual participants was waived because the study involved a hospital-level intervention that did not directly affect the clinical management of individual participants once diagnosed with a SARS-COV-2 infection.

Reviewing Editor

  1. Marc J Bonten, University Medical Center Utrecht, Netherlands

Publication history

  1. Received: March 11, 2022
  2. Accepted: August 25, 2022
  3. Accepted Manuscript published: September 13, 2022 (version 1)

Copyright

© 2022, Stirrup et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Oliver Stirrup
  2. James Blackstone
  3. Fiona Mapp
  4. Alyson MacNeil
  5. Monica Panca
  6. Alison Holmes
  7. Nicholas Machin
  8. Gee Yen Shin
  9. Tabitha Mahungu
  10. Kordo Saeed
  11. Tranprit Saluja
  12. Yusri Taha
  13. Nikunj Mahida
  14. Cassie Pope
  15. Anu Chawla
  16. Maria-Teresa Cutino-Moguel
  17. Asif Tamuri
  18. Rachel Williams
  19. Alistair Darby
  20. David L Robertson
  21. Flavia Flaviani
  22. Eleni Nastouli
  23. Samuel Robson
  24. Darren Smith
  25. Kenneth Laing
  26. Irene Monahan
  27. Beatrix Kele
  28. Sam Haldenby
  29. Ryan George
  30. Matthew Bashton
  31. Adam A Witney
  32. Matthew Byott
  33. Francesc Coll
  34. Michael Chapman
  35. Sharon J Peacock
  36. COG‐UK HOCI Investigators
  37. The COVID‐19 Genomics UK (COG‐UK) Consortium
  38. Joseph Hughes
  39. Gaia Nebbia
  40. David G Partridge
  41. Matthew Parker
  42. James Richard Price
  43. Christine Peters
  44. Sunando Roy
  45. Luke B Snell
  46. Thushan I de Silva
  47. Emma Thomson
  48. Paul Flowers
  49. Andrew Copas
  50. Judith Breuer
(2022)
Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: multicenter, prospective study
eLife 11:e78427.
https://doi.org/10.7554/eLife.78427
  1. Further reading

Further reading

    1. Epidemiology and Global Health
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    Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country.

    Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in eight of Brazil’s most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex- specific seroprevalence was estimated by correcting the crude seroprevalence by test sensitivity, specificity and antibody waning.

    Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma VOC was dominant, ranged from 19.3% (95% CrI 17.5% - 21.2%) in Curitiba to 75.0% (95% CrI 70.8% - 80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate (IHR) increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43 - 3.53).

    Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread.

    Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU Nº06531047/2020; JBS - Fazer o bem faz bem.

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