The Covid-19 pandemic has challenged public health systems throughout the world. Since October 2020, novel variants of concern of the SARS-CoV-2 virus have been identified and appear to be a significant concern for rates of infection, severity of disease, and the potential for variable responses to prior infection and/or vaccination. In the US—and especially in the state of New Hampshire—the number of SARS-CoV-2 genomes sequenced has been sparse. Furthermore, SARS-CoV-2 sequencing efforts have primarily been directed toward symptomatic individuals and/or contact tracing of special cases (e.g., hospital transmission). We currently lack knowledge in several areas including the temporal sequence and geolocation of the appearance of SARS-CoV-2 variants in regional communities; the correlation between incidents of viral outbreaks and SARS-CoV-2 variants; and the racial, ethnic, gender, and age susceptibility to infection (and severity of COVID-19 symptoms) by specific SARS-CoV-2 variants. In addition, as the U.S. enters a critical phase of the SARS-CoV-2 pandemic to develop herd immunity through prior infection and the vaccination program, we also lack an understanding of to what extent previously infected and/or vaccinated individuals are still susceptible to infection by SARS-CoV-2, and if so, what variants are infecting these supposedly “protected” individuals. The objective of this project is to determine the genomic sequence of a large majority of the SARS- CoV-2 variants identified in infected individuals in the state of NH and to apply this knowledge to better understand the likelihood that SARS-CoV-2 variants of concern increase the transmissibility of the virus, evade the immune systems of those previously infected, or result in a greater likelihood of infected individuals to experience clinical symptoms. The study population for this project consists of 12,000 stored human specimens previously confirmed by diagnostic tests to contain the SARS-CoV-2 virus, as well as newly identified specimens infected with SARS-CoV-2 as they become available during the project period. Preliminary whole-genome sequencing results document the quality of stored specimens as well as the ability to determine the lineage of SARS-CoV-2 variants present in the UNH congregate community and in the general NH population. Large-scale genomic surveillance of SARS-CoV-2 will permit correlating SARS-CoV-2 variant prevalence with available metadata (e.g., date of infection, geolocation, severity of outbreaks, symptomology, and characteristics of the sample population. Understanding the distribution and infectivity of SARS-CoV-2 variants will provide public health agencies with more accurate and specific information on public health measures that need to be enacted to control COVID-19 based on the types of SARS-CoV-2 variants present in specific populations, including those in congregate communities and previously infected individuals. The Covid-19 pandemic has challenged public health systems throughout the world, and recently emerging variants of concern further exacerbate efforts to control the spread of disease. The proposed research seeks to conduct extensive genomic surveillance of the variants of SARS-CoV-2 previously identified in infected individuals in the state of NH as well as newly occurring infections during the project period. Understanding the distribution and infectivity of SARS-CoV-2 variants will provide state and national public health agencies with more accurate and specific information on public health measures that need to be enacted to control COVID- 19 based on the types of SARS-CoV-2 variants present in specific populations.