Large-Scale Genomic Analysis of SARS-CoV-2 Omicron BA.5 Emergence, United States

The COVID-19 pandemic has been marked by continuous emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which those variants establish themselves in new geographic areas. We performed a discrete phylogeographic analysis on 18,529 sequences of the SARS-CoV-2 Omicron BA.5 sublineage sampled during February–June 2022 to elucidate emergence of that sublineage in different regions of the United States. The earliest BA.5 sublineage introductions came from Africa, the putative variant origin, but most were from Europe, matching a high volume of air travelers. In addition, we discovered extensive domestic transmission between different US regions, driven by population size and cross-country transmission between key hotspots. We found most BA.5 virus transmission within the United States occurred between 3 regions in the southwestern, southeastern, and northeastern parts of the country. Our results form a framework for analyzing emergence of novel SARS-CoV-2 variants and other pathogens in the United States.