High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States

Summary/Abstract SARS-CoV-2 is constantly evolving. Prior studies focused on high case-density locations, such as the U.S. Northern and Western metropolitan areas. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant, which was associated with higher genome copy numbers and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3' untranslated region. The data are consistent with community spread within local populations and the larger continental U.S. The data instill confidence in current testing sensitivity and validate "testing by sequencing" as an option to uncover cases, particularly non-standard COVID-19 clinical presentations. This study contributes to the understanding of COVID-19 through an extensive set of genomes from a non-urban setting and informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S.