Population-Based Severe Acute Respiratory Syndrome Coronavirus 2 Whole-Genome Sequencing and Contact Tracing During the Coronavirus Disease 2019 Pandemic in Switzerland

Background: Testing and contact tracing (CT) can interrupt transmission chains of SARS-CoV-2. Whole-genome sequencing (WGS) can potentially strengthen these investigations and provide insights on transmission.

Methods: We included all laboratory-confirmed COVID-19 cases diagnosed between 4 June and 26 July 2021, in a Swiss canton. We defined CT clusters based on epidemiological links reported in the CT data and genomic clusters as sequences with no single-nucleotide polymorphism (SNP) differences between any 2 pairs of sequences being compared. We assessed the agreement between CT clusters and genomic clusters.

Results: Of 359 COVID-19 cases, 213 were sequenced. Overall, agreement between CT and genomic clusters was low (Cohen's κ = 0.13). Of 24 CT clusters with ≥2 sequenced samples, 9 (37.5%) were also linked based on genomic sequencing but in 4 of these, WGS found additional cases in other CT clusters. Household was most often reported source of infection (n = 101 [28.1%]) and home addresses coincided well with CT clusters: In 44 of 54 CT clusters containing ≥2 cases (81.5%), all cases in the cluster had the same reported home address. However, only a quarter of household transmission was confirmed by WGS (6 of 26 genomic clusters [23.1%]). A sensitivity analysis using ≤1-SNP differences to define genomic clusters resulted in similar results.

Conclusions: WGS data supplemented epidemiological CT data, supported the detection of potential additional clusters missed by CT, and identified misclassified transmissions and sources of infection. Household transmission was overestimated by CT.