Project Summary The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic that has currently caused over 30 million illnesses and 550,000 deaths in the United States. Variants that show changes in transmissibility (B.1.1.7 variant) and antigenic recognition (B.1.35 and P.1 variants) have recently emerged. The impact of these variants on immune and non-immune populations remains unknown. Within South Dakota, high rates of SARS-CoV-2 infections have occurred since the start of the pandemic, resulting in extra stress on our healthcare infrastructure, especially in our medically underserved communities. In direct response to the Notice of Special Interest (NOSI): Urgent Competitive Revisions to IDeA and NARCH Programs for SARS-CoV-2 Surveillance Studies, the current supplement proposes expanding our efforts in SARS-CoV-2 surveillance. Specifically, next-generation sequencing will be conducted on the clinical samples to increase our surveillance efforts, including in the tourism-heavy western portion of South Dakota. To achieve our research goals, a subset of clinical samples collected in South Dakota will be sequenced each month. These sequences will be used to determine how the incidence of variants in South Dakota counties relates to the number of cases over time. The goal is to determine whether a particular variant is associated with outbreak events within distinct geographical locations and specific times. The resulting findings will help advance research on the spread and evolution of the SARS-CoV-2 virus in underserved communities throughout the state. These findings will provide critical information regarding circulating variants in areas of the underserved Midwest that are expected to see significant increases in tourism in the coming months.