Pham, K.; Chaguza, C.; Lopes, R.; Cohen, T.; Taylor-Salmon, E.; Wilkinson, M.; Katebi, V.; Grubaugh, N. D.; Hill, V.

The COVID-19 pandemic is marked by the continuing emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which these lineages establish themselves in new geographical areas. In this study, we performed a discrete phylogeographic analysis on ~19,000 SARS-CoV-2 sequences of Omicron BA.5 lineages between February and June 2022 to better understand how it emerged in different regions of the United States (U.S.). We found that the earliest introductions came from Africa, the putative origin of the variant, but the majority were from Europe, correlating with the high volume of air travelers. Additionally, the analysis revealed extensive domestic transmission between different regions of the U.S. driven by population size and cross-country transmission. Results suggest that most of the within-U.S. spread was between three regions that include California, New York, and Florida. Our results form a framework for understanding novel SARS-CoV-2 variant emergence in the U.S.