High-Density Amplicon Sequencing Identifies Community Spread and Ongoing Evolution of SARS-CoV-2 in the Southern United States

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving. Prior studies focused on high-case-density locations, such as the northern and western metropolitan areas of the United States. This study demonstrates continued SARS-CoV-2 evolution in a suburban southern region of the United States by high-density amplicon sequencing of symptomatic cases. 57% of strains carry the spike D614G variant, which is associated with higher genome copy numbers, and its prevalence expands with time. Four strains carry a deletion in a predicted stem loop of the 3′ UTR. The data are consistent with community spread within local populations and the larger continental United States. The data instill confidence in current testing sensitivity and validate “testing by sequencing” as an option to uncover cases, particularly nonstandard coronavirus disease 2019 (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 United States.
Graphical Abstract
Highlights • NGS of SARS-CoV-2 from a rural/suburban area shows local spread as an epidemic driver • The D614G spike mutant is observed in >50% of cases • Deletion in the 3′ UTR of SARS-CoV-2 is identified • Targeted NGS has 100% specificity and is as sensitive as qPCR
McNamara et al. use next-generation sequencing (NGS) with a high-density tiling array across SARS-CoV-2 to find a deletion and document how the D614G spike protein mutation rapidly swept through a rural/suburban population. D614G is associated with slightly higher viral loads.