Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study

Abstract

Background: There is ongoing uncertainty regarding transmission chains and the respective roles of healthcare workers (HCWs) and elderly patients in nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in geriatric settings.

Methods: We performed a retrospective cohort study including patients with nosocomial coronavirus disease 2019 (COVID-19) in four outbreak-affected wards, and all SARS-CoV-2 RT-PCR positive HCWs from a Swiss university-affiliated geriatric acute-care hospital that admitted both Covid-19 and non-Covid-19 patients during the first pandemic wave in Spring 2020. We combined epidemiological and genetic sequencing data using a Bayesian modelling framework, and reconstructed transmission dynamics of SARS-CoV-2 involving patients and HCWs, to determine who infected whom. We evaluated general transmission patterns according to case type (HCWs working in dedicated Covid-19 cohorting wards: HCWcovid; HCWs working in non-Covid-19 wards where outbreaks occurred: HCWoutbreak; patients with nosocomial Covid-19: patientnoso) by deriving the proportion of infections attributed to each case type across all posterior trees and comparing them to random expectations.

Results: During the study period (March 1 to May 7, 2020) we included 180 SARS-CoV-2 positive cases: 127 HCWs (91 HCWcovid, 36 HCWoutbreak) and 53 patients. The attack rates ranged from 10-19% for patients, and 21% for HCWs. We estimated that 16 importation events occurred with high confidence (four patients, 12 HCWs) that jointly led to up to 41 secondary cases; in six additional cases (five HCWs, one patient), importation was possible with a posterior between 10-50%. Most patient-to-patient transmission events involved patients having shared a ward (95.2%, 95% credible interval [CrI] 84.2-100%), in contrast to those having shared a room (19.7%, 95%CrI 6.7-33.3%). Transmission events tended to cluster by case type: patientnoso were almost twice as likely to be infected by other patientnoso than expected (observed:expected ratio 2.16, 95%CrI 1.17 - 4.20, p = 0.006); similarly, HCWoutbreak were more than twice as likely to be infected by other HCWoutbreak than expected (2.72, 95%CrI 0.87-9.00, p = 0.06). The proportion of infectors being HCWcovid was as expected as random. We found a trend toward a greater proportion of high transmitters (≥2 secondary cases) among HCWoutbreak than patientnoso in the late phases (28.6% vs. 11.8%) of the outbreak, although this was not statistically significant.

Conclusions: Most importation events were linked to HCW. Unexpectedly, transmission between HCWcovid was more limited than transmission between patients and HCWoutbreak. This finding highlights gaps in infection control and suggests possible areas of improvements to limit the extent of nosocomial transmission.

Funding: This work was supported by a grant from the Swiss National Science Foundation under the NRP78 funding scheme (Grant no. 4078P0_198363).

Data availability

Due to small size of the various clusters, the raw clinical data will not be shared to safeguard anonymity of patients and healthcare workers. Processed data of the output of the model, which will comprise the posterior distribution of infectors, will be made available in an anonymized version. This will allow reproducing the analyses looking at the proportion of healthcare workers among infectors, and the number of secondary infections. This data will not allow reconstruction of the transmission tree, which would require the raw data. The raw data in an anonymized format will be made available upon reasonable and justified request, subject to approval by the project's Senior Investigator. The genomic sequencing data have been submitted to the Genbank repository (GenBank accession numbers: ON209723-ON209871).

Article and author information

Author details

  1. Mohamed Abbas

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    For correspondence
    mohamed.abbas@hcuge.ch
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7265-1887
  2. Dr Anne Cori

    MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
    Competing interests
    Dr Anne Cori, received honoraria (which was paid to the institution) from Pfizer for lecturing on a course on mathematical modelling of infectious disease transmission and vaccination book. The author has no other competing interests to declare..
  3. Samuel Cordey

    Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2684-5680
  4. Florian Laubscher

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  5. Tomás Robalo Nunes

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  6. Ashleigh Myall

    Department of Infectious Diseases, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Julien Salamun

    Department of Primary Care, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  8. Philippe Huber

    Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  9. Dina Zekry

    Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  10. Virginie Prendki

    Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  11. Anne Iten

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  12. Laure Vieux

    Occupational Health Service, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  13. Valérie Sauvan

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  14. Christophe E Graf

    Occupational Health Service, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  15. Stephan Harbarth

    Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland
    Competing interests
    No competing interests declared.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (4078P0_198363)

  • Mohamed Abbas
  • Dr Anne Cori
  • Samuel Cordey
  • Florian Laubscher
  • Tomás Robalo Nunes
  • Anne Iten
  • Stephan Harbarth

National Institute for Health Research Health Protection Research Unit (NIHR200908)

  • Mohamed Abbas
  • Dr Anne Cori

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

Ethics

Human subjects: The Ethics Committee of the Canton of Geneva (CCER), Switzerland, approved this study (CCER no. 2020-01330 and CCER no. 2020-00827). Written informed consent was obtained from HCWs. Written informed consent was not required for patients as data were generated in a context of mandatory surveillance.

Reviewing Editor

  1. Joshua T Schiffer, Fred Hutchinson Cancer Research Center, United States

Version history

  1. Received: January 6, 2022
  2. Preprint posted: January 10, 2022 (view preprint)
  3. Accepted: July 3, 2022
  4. Accepted Manuscript published: July 19, 2022 (version 1)
  5. Version of Record published: July 27, 2022 (version 2)

Copyright

© 2022, Abbas 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. Mohamed Abbas
  2. Dr Anne Cori
  3. Samuel Cordey
  4. Florian Laubscher
  5. Tomás Robalo Nunes
  6. Ashleigh Myall
  7. Julien Salamun
  8. Philippe Huber
  9. Dina Zekry
  10. Virginie Prendki
  11. Anne Iten
  12. Laure Vieux
  13. Valérie Sauvan
  14. Christophe E Graf
  15. Stephan Harbarth
(2022)
Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: a combined retrospective epidemiological and genomic study
eLife 11:e76854.
https://doi.org/10.7554/eLife.76854

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https://doi.org/10.7554/eLife.76854

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