SARS-CoV-2 Outbreak Investigation Using Contact Tracing and Whole-Genome Sequencing in an Ontario Tertiary Care Hospital

Abstract

Genomic epidemiology can facilitate an understanding of evolutionary history and transmission dynamics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. We used next-generation sequencing techniques to study SARS-CoV-2 genomes isolated from patients and health care workers (HCWs) across five wards of a Canadian hospital with an ongoing SARS-CoV-2 outbreak. Using traditional contact tracing methods, we show transmission events between patients and HCWs, which were also supported by the SARS-CoV-2 lineage assignments. The outbreak predominantly involved SARS-CoV-2 B.1.564.1 across all five wards, but we also show evidence of community introductions of lineages B.1, B.1.1.32, and B.1.231, falsely assumed to be outbreak related. Altogether, our study exemplifies the value of using contact tracing in combination with genomic epidemiology to understand the transmission dynamics and genetic underpinnings of a SARS-CoV-2 outbreak. IMPORTANCE Our manuscript describes a SARS-CoV-2 outbreak investigation in an Ontario tertiary care hospital. We use traditional contract tracing paired with whole-genome sequencing to facilitate an understanding of the evolutionary history and transmission dynamics of this SARS-CoV-2 outbreak in a clinical setting. These advancements have enabled the incorporation of phylogenetics and genomic epidemiology into the understanding of clinical outbreaks. We show that genomic epidemiology can help to explore the genetic evolution of a pathogen in real time, enabling the identification of the index case and helping understand its transmission dynamics to develop better strategies to prevent future spread of SARS-CoV-2 in congregate, clinical settings such as hospitals.

Keywords: COVID-19; Canada; DNA sequencing; SARS-CoV-2; contact tracing; genomics; hospital; outbreak.

FIG 1

Ward attribution and SARS-CoV-2 lineage variant descriptions of the positive COVID-19 patient and HCW cases. COVID-positive cases that were considered importations from the community into the hospital based on lineage assignment alone are indicated as CI. Arrows depict the duration of time of COVID-positive patient and/or HCW cases within a ward. All 58 patients and 14/48 HCWs had known COVID-positive test dates.

FIG 2

Visual illustration of the COVID-positive patient cases in wards A to E. The number beside each of the viruses indicates the date in December 2020 that the patient sample returned positive for COVID-19 (e.g., 3 indicates 3 December 2020). Diagrams of each of the wards are not to scale. The asterisk indicates a COVID-19-positive case that was confirmed on 17 December 2020 but is either attributed to room 17 or room 7, which already had a sequenced COVID-19-positive case (7 December 2020). Information on the outbreak based on classical epidemiology (e.g., known contact events) is described by the patient and health care worker (HCW) symbols. A COVID-positive physiotherapist was known to move between wards A and B, but directionality of transmission is unclear. Four ward C patients were in contact with two COVID-positive (COVID+) ward A patients. There were no known exposure events in ward D. All 4 patients in ward E were exposed to one COVID-positive HCW, but only 3/4 patients had their COVID sample sequenced, which is depicted in the diagram.

FIG 3

Phylogenetic tree (A) and minimum spanning tree (B) with the scales in nucleotide distances of outbreak samples and Canadian SARS-CoV-2 B.1.564.1 sequences from GISAID. Sequences from GISAID are shown in green, whereas sequences from the outbreak are shown in blue. The size of the circle in the minimum spanning tree is proportional to the number of sequences.

FIG 4

Time tree (A) and divergence tree (B) generated using only SARS-CoV-2 B.1.564.1 outbreak samples annotated with personnel and ward. Branch length corresponds to time and the number of mutations for the time and divergence tree, respectively. Sample source (e.g., health care workers [HCWs] or patients) and ward information from patients only are annotated beside each tree.