The goal of this project is to leverage the extensive COVID-19 testing program at Clemson University (CU) to detect and monitor emerging variants of the SARS-CoV2 virus by sequencing every positive sample. Variants of concern are emerging in our state of South Carolina. This is a serious public health threat because there is a real risk that these new variants may escape the coverage of recently developed COVID-19 vaccines or infect previously exposed individuals. This sequencing project will provide much-needed insight and guidance to inform policy decisions in our region and elsewhere to help mitigate these potential threats. In Fall 2020, CU established the new CLIA-certified Clemson Research and Education in Disease Diagnosis and Intervention (REDDI) Lab. In what has become one of the robust COVID-19 testing programs in the country, the REDDI Lab tests of all university personnel and students at least once a week with their own highly accurate saliva COVID-19 RT-PCR test, developed and validated by researchers at Clemson shortly after the start of the pandemic. The lab also provides free testing to members of the surrounding upstate SC community. It processes 99.9% of its tests within 24hrs and currently averages over 20,000 tests per week, a substantial fraction of all testing in the state. We propose the following aims: Aim 1: Implement a SARS-CoV2 genomic sequencing workflow and a data collection system to use a large established COVID-19 testing program in rural, upstate South Carolina. Aim 2: Determine the association of SARS-CoV2 genomic variants with population demographics, outbreak events, COVID-19 symptom severity and duration, previous infection, and vaccination. Given the capabilities of the REDDI Lab and the state-of-the-art Clemson University Genomics and Bioinformatics Facility (CUGBF), we are ideally positioned to build a robust and informative sequencing and surveillance program. Due to proximity to major travel hubs (Charlotte / Atlanta) and the transient nature of a university population, many variants will likely appear in our testing pool. More importantly, we will capture data from patient demographic groups that are highly under-sampled by other labs at hospitals and public health agencies. Unlike many of these COVID testing programs, the majority of positive cases detected by our lab are from younger patients (students) who are asymptomatic or minimally symptomatic at the time of diagnosis. In addition, the Clemson public health initiatives partnering with our testing lab include free daily testing for the community using a standing site in the city of Clemson and a mobile testing van that provides outreach to disadvantaged areas of the Upstate where COVID-19 testing is not easily available. Our community testing population is an excellent representation of the Upstate SC demographics, including significant numbers of patients from populations with known COVID-19 outcome disparities. The goal of this project is to leverage the extensive COVID-19 testing program at Clemson University to detect and monitor emerging variants of the SARS-CoV2 virus by sequencing every positive sample. Variants of concern of SARS-CoV-2 have been rapidly emerging in our state of South Carolina. This poses a serious public health threat because there is a real risk that these new variants may escape the coverage of recently developed COVID-19 vaccines or infect previously exposed individuals. This sequencing project will provide much-needed insight and guidance to inform policy decisions in our region and elsewhere to help mitigate these potential threats.