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Enhancing epidemiological investigation of nosocomial SARS-CoV-2 infection with whole genome sequencing: A retrospective cohort study across four hospitals in the UK.

By Sheila F Lumley, Bede Constantinides, Nicholas Sanderson, Gillian Rodger, Teresa L Street, Jeremy Swann, Kevin K Chau, Denise O'Donnell, Fiona Warren, Sarah Hoosdally, OUH Microbiology laboratory, OUH Infection Prevention and Control team, Anne-Marie O'Donnell, Timothy M Walker, Nicole E Stoesser, Lisa Butcher, Tim EA Peto, Derrick W Crook, Katie Jeffery, Philippa C Matthews, David W Eyre

Posted 02 Jul 2021
medRxiv DOI: 10.1101/2021.06.28.21259028

Background Despite robust efforts, patients and staff acquire SARS-CoV-2 infection in hospitals. In this retrospective cohort study, we investigated whether whole-genome sequencing (WGS) could enhance the epidemiological investigation of healthcare-associated SARS-CoV-2 acquisition. Methods and findings From 17-November-2020 to 5-January-2021, 803 inpatients and 329 staff were diagnosed with SARS-CoV-2 infection across four teaching hospitals in Oxfordshire, UK. We classified cases according to epidemiological definitions, sought epidemiological evidence of a potential source for each nosocomial infection, and evaluated if epidemiologically-linked cases had genomic evidence supporting transmission. We compared epidemiological and genomic outbreak identification. Using 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: 107/109(98%) had a prior-negative PCR in the same hospital stay before testing positive, and 101(93%) shared time and space with known infected patients/staff. 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. WGS highlighted SARS-CoV-2 is mainly imported into hospitals: 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. Hospitals not routinely admitting COVID-19 patients had low rates of transmission. Undiagnosed/unsequenced individuals prevent genomic data from excluding nosocomial acquisition. Conclusions Our findings suggest current surveillance definitions underestimate nosocomial acquisition and reveal most nosocomial transmission occurs from a relatively limited number of highly infectious individuals.

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