Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study

Abstract

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034(11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45-6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99-3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07-2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28-0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25-2.21]) and Asian (1.51 [1.28-1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34-3.15]).

Data availability

The data studied are available from the Infections in Oxfordshire Research Database (https://oxfordbrc.nihr.ac.uk/research-themes-overview/antimicrobial-resistance-and-modernising-microbiology/infections-in-oxfordshire-research-database-iord/), subject to an application and research proposal meeting the ethical and governance requirements of the Database. For further details on how to apply for access to the data and for a research proposal template please email iord@ndm.ox.ac.uk.

Article and author information

Author details

  1. David W Eyre

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    For correspondence
    david.eyre@bdi.ox.ac.uk
    Competing interests
    David W Eyre, Lecture fees from Gilead, outside the submitted work.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5095-6367
  2. Sheila F Lumley

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Denise O'Donnell

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Mark Campbell

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Elizabeth Sims

    Occupational Health, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Elaine Lawson

    Occupational Health, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  7. Fiona Warren

    Occupational Health, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  8. Tim James

    Clinical Biochemstry, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  9. Stuart Cox

    Clinical Biochemistry, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  10. Alison Howarth

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  11. George Doherty

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  12. Stephanie B Hatch

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  13. James Kavanagh

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  14. Kevin K Chau

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  15. Philip W Fowler

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0912-4483
  16. Jeremy Swann

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  17. Denis Volk

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  18. Fan Yang-Turner

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  19. Nicole Stoesser

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4508-7969
  20. Philippa C Matthews

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  21. Maria Dudareva

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  22. Timothy Davies

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  23. Robert H Shaw

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  24. Leon Peto

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  25. Louise O Downs

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  26. Alexander Vogt

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  27. Ali Amini

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  28. Bernadette C Young

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6071-6770
  29. Philip George Drennan

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3367-3335
  30. Alexander J Mentzer

    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4502-2209
  31. Donal T Skelly

    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2426-3097
  32. Fredrik Karpe

    NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  33. Matt J Neville

    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6004-5433
  34. Monique Andersson

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  35. Andrew J Brent

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  36. Nicola Jones

    Clinical infection, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  37. Lucas Martins Ferreira

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  38. Thomas Christott

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  39. Brian D Marsden

    NDM, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1937-4091
  40. Sarah Hoosdally

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  41. Richard Cornall

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  42. Derrick W Crook

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0590-2850
  43. David I Stuart

    Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  44. Gavin Screaton

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  45. Oxford University Hospitals Staff Testing Group

  46. Timothy EA Peto

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  47. Bruno Holthof

    Corporate, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  48. Anne-Marie O'Donnell

    Occupational Health, Oxford University Hospitals, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  49. Daniel Ebner

    Target Discovery Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6495-7026
  50. Christopher P Conlon

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  51. Katie Jeffery

    Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  52. Timothy M Walker

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.

Funding

UK Government: Department of Health and Social Care

  • David W Eyre
  • Sheila F Lumley
  • Denise O'Donnell
  • Mark Campbell
  • Elizabeth Sims
  • Elaine Lawson
  • Fiona Warren
  • Tim James
  • Stuart Cox
  • Alison Howarth
  • George Doherty
  • Stephanie B Hatch
  • James Kavanagh
  • Kevin K Chau
  • Philip W Fowler
  • Jeremy Swann
  • Denis Volk
  • Fan Yang-Turner
  • Nicole Stoesser
  • Philippa C Matthews
  • Maria Dudareva
  • Timothy Davies
  • Robert H Shaw
  • Leon Peto
  • Louise O Downs
  • Alexander Vogt
  • Ali Amini
  • Bernadette C Young
  • Philip George Drennan
  • Alexander J Mentzer
  • Donal T Skelly
  • Fredrik Karpe
  • Matt J Neville
  • Monique Andersson
  • Andrew J Brent
  • Nicola Jones
  • Lucas Martins Ferreira
  • Thomas Christott
  • Brian D Marsden
  • Sarah Hoosdally
  • Richard Cornall
  • Derrick W Crook
  • David I Stuart
  • Gavin Screaton
  • Timothy EA Peto
  • Bruno Holthof
  • Anne-Marie O'Donnell
  • Daniel Ebner
  • Christopher P Conlon
  • Katie Jeffery
  • Timothy M Walker

Wellcome Trust Clinical Research Training Fellow (216417/Z/19/Z)

  • Ali Amini

NIHR Clinical Lecturer

  • Bernadette C Young

Structural Genomics Consortium

  • Lucas Martins Ferreira
  • Thomas Christott
  • Brian D Marsden

Kennedy Trust for Rheumatology Research

  • Brian D Marsden

Wellcome Trust Senior Investigator

  • Gavin Screaton

Schmidt Foundation

  • Gavin Screaton

Wellcome Trust Career Development Fellow (214560/Z/18/Z)

  • Timothy M Walker

National Institute of Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (HPRU-2012-10041)

  • David W Eyre
  • Sheila F Lumley
  • Denise O'Donnell
  • Mark Campbell
  • Elizabeth Sims
  • Elaine Lawson
  • Fiona Warren
  • Tim James
  • Stuart Cox
  • Alison Howarth
  • George Doherty
  • Stephanie B Hatch
  • James Kavanagh
  • Kevin K Chau
  • Philip W Fowler
  • Jeremy Swann
  • Denis Volk
  • Fan Yang-Turner
  • Nicole Stoesser
  • Philippa C Matthews
  • Maria Dudareva
  • Timothy Davies
  • Robert H Shaw
  • Leon Peto
  • Louise O Downs
  • Alexander Vogt
  • Ali Amini
  • Bernadette C Young
  • Philip George Drennan
  • Alexander J Mentzer
  • Donal T Skelly
  • Fredrik Karpe
  • Matt J Neville
  • Monique Andersson
  • Andrew J Brent
  • Nicola Jones
  • Lucas Martins Ferreira
  • Thomas Christott
  • Brian D Marsden
  • Sarah Hoosdally
  • Richard Cornall
  • Derrick W Crook
  • David I Stuart
  • Gavin Screaton
  • Timothy EA Peto
  • Bruno Holthof
  • Anne-Marie O'Donnell
  • Daniel Ebner
  • Christopher P Conlon
  • Katie Jeffery
  • Timothy M Walker

Robertson Foundation

  • David W Eyre

NIHR Oxford BRC Senior Fellow

  • David W Eyre
  • Philippa C Matthews

Wellcome Trust Clinical Research Fellow

  • Sheila F Lumley

Medical Research Council (MR/N00065X/1)

  • David I Stuart

Wellcome Trust Intermediate Fellowship (110110/Z/15/Z)

  • Philippa C Matthews

NIHR Doctoral Research Fellow

  • Maria Dudareva

Medical Research Foundation (MRF-145-004-TPG-AVISO)

  • Kevin K Chau

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

Ethics

Human subjects: All asymptomatic staff data collection and testing were part of enhanced hospital infection prevention and control measures instituted by the UK Department of Health and Social Care (DHSC). Deidentified data from staff testing and patients were obtained from the Infections in Oxfordshire Research Database (IORD) which has generic Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group approvals (19/SC/0403, ECC5-017(A)/2009). De-identified patient data extracted included admission and discharge dates, ward location and positive Covid-19 test results.

Reviewing Editor

  1. Marc Lipsitch, Harvard TH Chan School of Public Health, United States

Publication history

  1. Received: July 2, 2020
  2. Accepted: August 18, 2020
  3. Accepted Manuscript published: August 21, 2020 (version 1)
  4. Version of Record published: September 11, 2020 (version 2)

Copyright

© 2020, Eyre 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. David W Eyre
  2. Sheila F Lumley
  3. Denise O'Donnell
  4. Mark Campbell
  5. Elizabeth Sims
  6. Elaine Lawson
  7. Fiona Warren
  8. Tim James
  9. Stuart Cox
  10. Alison Howarth
  11. George Doherty
  12. Stephanie B Hatch
  13. James Kavanagh
  14. Kevin K Chau
  15. Philip W Fowler
  16. Jeremy Swann
  17. Denis Volk
  18. Fan Yang-Turner
  19. Nicole Stoesser
  20. Philippa C Matthews
  21. Maria Dudareva
  22. Timothy Davies
  23. Robert H Shaw
  24. Leon Peto
  25. Louise O Downs
  26. Alexander Vogt
  27. Ali Amini
  28. Bernadette C Young
  29. Philip George Drennan
  30. Alexander J Mentzer
  31. Donal T Skelly
  32. Fredrik Karpe
  33. Matt J Neville
  34. Monique Andersson
  35. Andrew J Brent
  36. Nicola Jones
  37. Lucas Martins Ferreira
  38. Thomas Christott
  39. Brian D Marsden
  40. Sarah Hoosdally
  41. Richard Cornall
  42. Derrick W Crook
  43. David I Stuart
  44. Gavin Screaton
  45. Oxford University Hospitals Staff Testing Group
  46. Timothy EA Peto
  47. Bruno Holthof
  48. Anne-Marie O'Donnell
  49. Daniel Ebner
  50. Christopher P Conlon
  51. Katie Jeffery
  52. Timothy M Walker
(2020)
Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study
eLife 9:e60675.
https://doi.org/10.7554/eLife.60675
  1. Further reading

Further reading

    1. Epidemiology and Global Health
    2. Genetics and Genomics
    Amy L Roberts, Alessandro Morea ... Kerrin S Small
    Research Article

    Background:

    Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown.

    Methods:

    We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis.

    Results:

    We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence.

    Conclusions:

    Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.

    Funding:

    KSS acknowledges funding from the Medical Research Council [MR/M004422/1 and MR/R023131/1]. JTB acknowledges funding from the ESRC [ES/N000404/1]. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.

    1. Epidemiology and Global Health
    2. Immunology and Inflammation
    James A Hay, Stephen M Kissler ... Yonatan H Grad
    Research Article

    Background: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

    Methods: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

    Results: Among individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.3-53.6%) remained potentially infectious (Ct<30) five days post detection, with small differences across variants and vaccination status. Only seven viral rebounds (0.7%; N=999) were observed, with rebound defined as 3+ days with Ct<30 following an initial clearance of 3+ days with Ct≥30. High antibody titers against the founder SARS-CoV-2 strain predicted lower peak viral loads and shorter durations of infection. Among Omicron BA.1 infections, boosted individuals had lower pre-booster antibody titers and longer clearance times than non-boosted individuals.

    Conclusions: SARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines.

    Funding: Supported in part by CDC contract #200-2016-91779, a sponsored research agreement to Yale University from the National Basketball Association contract #21-003529, and the National Basketball Players Association.