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 hours 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.
Competing Interest Statement
The authors have declared no competing interest.
COG-UK HOCI is funded by the COG-UK consortium, which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. JBr receives funding from the NIHR ULC/UCLH Biomedical Research Centre. FC is funded by Wellcome (grant number: 201344/Z/16/Z). MDP is funded by the NIHR Sheffield Biomedical Research Centre (BRC – IS-BRC-1215-20017). No additional payments, funding or services were received from third parties.
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Research Ethics for COG-UK was granted by the PHE Research Ethics and Governance group as part of the emergency response to COVID-19 (24 April 2020, REF: R&D NR0195).
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
The sequence data analysed are included within publicly available datasets. However, due to data governance restrictions it is not possible to openly share the associated meta-data for the analysis described.