Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data

Author:

Stirrup Oliver1ORCID,Hughes Joseph2,Parker Matthew345,Partridge David G67ORCID,Shepherd James G2,Blackstone James8,Coll Francesc9,Keeley Alexander67,Lindsey Benjamin B67ORCID,Marek Aleksandra10,Peters Christine10,Singer Joshua B2,Tamuri Asif11,de Silva Thushan I67,Thomson Emma C21213,Breuer Judith14ORCID,

Affiliation:

1. Institute for Global Health, University College London, London, United Kingdom

2. MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom

3. Sheffield Bioinformatics Core, The University of Sheffield, Sheffield, United Kingdom

4. Sheffield Institute for Translational Neuroscience, The University of Sheffield, Sheffield, United Kingdom

5. Sheffield Biomedical Research Centre, The University of Sheffield, Sheffield, United Kingdom

6. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom

7. The Florey Institute for Host-Pathogen Interactions & Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, United Kingdom

8. The Comprehensive Clinical Trials Unit at UCL , University College London, London, United Kingdom

9. Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom

10. Clinical Microbiology, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom

11. Research Computing, University College London, London, United Kingdom

12. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

13. Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, United Kingdom

14. Division of Infection and Immunity, University College London, London, United Kingdom

Abstract

Background:Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult.Methods:We developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hr following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February–May 2020.Results:We analysed data from 326 HOCIs. Among HOCIs with time from admission ≥8 days, the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time from admission 3–7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%).Conclusions:The methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period.Funding:COG-UK HOCI funded by COG-UK consortium, supported by funding from UK Research and Innovation, National Institute of Health Research and Wellcome Sanger Institute.

Funder

Wellcome

NIHR

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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