Viral genomic surveillance is critical for identification of SARS-CoV-2 variants that exhibit biological characteristics of concern for public health, such as escape from humoral immunity, enhanced transmissibility, and/or increased pathogenic potential. This competitive revision proposal represents a collaboration between two LSU Health Shreveport (LSUHS) CoBRE’s (Center for Redox Biology and Cardiovascular Disease [CRBCD] and Center for Applied Immunology and Pathological Processes [CAIPP]) and leverages established institutional programs including the Center for Emerging Viral Threats’ (CEVT) CLIA/CAP certified reference laboratory, ongoing COVID-19 clinical research, community mass vaccination and testing services, and a highly productive viral genome sequencing program that have served North and Central Louisiana throughout the pandemic. Additionally, LSUHS is in active partner with the Louisiana Department of Health (LDH) for these efforts and has a strong foundation for translation of viral genomic surveillance data into favorable public health outcomes, such as protection of vulnerable communities and targeted mitigation steps against variants of concern. As such, this competitive revision supplement will pursue the following two specific aims: Aim 1) Establish rapid SARS-CoV-2 viral genome sequencing and data sharing prioritized by re-infections and infections of vaccine recipients; and Aim 2) Perform SARS-CoV-2 viral genome sequencing and data sharing of moderate to severe COVID-19 patients with predisposing risk factors and/or cardiopulmonary complications. Together, this work will greatly enhance genomic surveillance of SARS-CoV-2 in Louisiana, East Texas, and Southern Arkansas to benefit US public health and advance research regarding this devastating virus.  The SARS-CoV-2 pandemic has had a devastating impact on the health and wellbeing of the U.S. and world along with significant social and economic harm to many individuals with disproportionate circumstances. Importantly, genomic sequencing of SARS-CoV-2 for unique variants is essential to help mitigate these massive negative impacts and to aid in facilitating vaccination efforts to control the virus. Work in this competitive revision application will provide critical viral genomic sequencing for SARS-CoV-2 across North and Central Louisiana that is essential for public health needs in response to the pandemic.