Viral Genome Sequencing to Decipher In-Hospital SARS-CoV-2 Transmission Events

Abstract

Abstract Background: The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. Objectives: To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission Methods: 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Results: Clustering analysis of 619 viral genomes generated 18 clusters ranging from 3 to 29 individuals. Sequencing-based transmission clusters showed little overlap to those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n=681), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Conclusion: Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies across the world, advocate for viral genome sequencing as pathogen transmission surveillance tools in hospitals.