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ObjectivesDespite robust efforts, patients and staff acquire SARS-CoV-2 infection in hospitals. We investigated whether whole-genome sequencing enhanced the epidemiological investigation of healthcare-associated SARS-CoV-2 acquisition.MethodsFrom 17-November-2020 to 5-January-2021, 803 inpatients and 329 staff were diagnosed with SARS-CoV-2 infection at four Oxfordshire hospitals. We classified cases using epidemiological definitions, looked for a potential source for each nosocomial infection, and evaluated genomic evidence supporting transmission.ResultsUsing national epidemiological definitions, 109/803(14%) inpatient infections were classified as definite/probable nosocomial, 615(77%) as community-acquired and 79(10%) as indeterminate. There was strong epidemiological evidence to support definite/probable cases as nosocomial. Many indeterminate cases were likely infected in hospital: 53/79(67%) had a prior-negative PCR and 75(95%) contact with a potential source. 89/615(11% of all 803 patients) with apparent community-onset had a recent hospital exposure. Within 764 samples sequenced 607 genomic clusters were identified (>1 SNP distinct). Only 43/607(7%) clusters contained evidence of onward transmission (subsequent cases within ≤ 1 SNP). 20/21 epidemiologically-identified outbreaks contained multiple genomic introductions. Most (80%) nosocomial acquisition occurred in rapid super-spreading events in settings with a mix of COVID-19 and non-COVID-19 patients.ConclusionsCurrent surveillance definitions underestimate nosocomial acquisition. Most nosocomial transmission occurs from a relatively limited number of highly infectious individuals.

Original publication




Journal article


The Journal of infection

Publication Date



John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust etc.; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Oxford, United Kingdom. Electronic address:


OUH Microbiology laboratory, OUH Infection Prevention and Control team