SARS-CoV-2 Genomic Diversity in Households Highlights the Challenges of Sequence-Based Transmission Inference
Emily E. Bendall, Gabriela Paz‐Bailey, Gilberto A. Santiago, Christina A. Porucznik, Joseph B. Stanford, Melissa S. Stockwell, Jazmin Duque, Zuha Jeddy, Vic Veguilla, Chelsea G. Major, Vanessa Rivera‐Amill, Melissa A. Rolfes, Fatimah S. Dawood, Adam S. Lauring
Abstract
We performed whole-genome sequencing of SARS-CoV-2 from prospectively identified cases in three longitudinal household cohorts. In a majority of multi-infection households, SARS-CoV-2 consensus sequences were indistinguishable, and they differed by 1 to 2 mutations in the rest. Importantly, even with modest genomic surveillance of the community (3 to 5% of cases sequenced), it was not uncommon to find community sequences interspersed with household sequences on phylogenetic trees. Identification of shared minority variants only occasionally resolved these ambiguities in transmission linkage. Overall, the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Our work highlights the need to carefully consider both epidemiologic linkage and sequence data to define transmission chains in households, hospitals, and other transmission settings.