Abstract Frequent emergence of new SARS-CoV-2 variants is keeping us on alert and requiring a through surveillance of circulating variants, to trace and track the introduction of unusual variants with a potential to cause public health problems. During the past two years, we witnessed the emergence of quite a few variants of concerns (VOCs), which have the ability to evade immune protection, acquired through vaccination/natural infection as well as enhanced infectivity and transmissibility. The identification of all VOCs has been possible through a continuous genomic surveillance and whole genome sequencing (WGS) of SARS-CoV-2. Therefore, adapting a comprehensive SARS-CoV-2 sequencing approach from a large proportion of positive tested individuals will help in identifying variants early and managing resources to minimize the spread of SARS-CoC- 2. The major goal of this application is to track the dynamics of variants as well as the evolution of any unusual variants through sequencing of SARS-CoV-2 positive specimens. We have been monitoring SARS-CoV-2 variants in the state of Nevada with particular focus on variants circulating in the Washoe and surrounding counties of Northern Nevada. We reported the cases of SARS-CoV-2 reinfection, progression of Delta and Omicron variants overtime after detecting the first cases of respective variants in NV. Our sequencing efforts from the last year strongly supports that we have the capacity to successfully determine the dynamics of SARS-CoV-2 and address these epidemiologic questions: 1) Whether different variants are prevalent among different racial/ethnic and age groups or responsible for different COVID-19 symptoms manifestations? 2) Determine the number of cases caused by different variants and the dynamics of their change over, to define the transmissibility in the study population. We are using innovative approaches, of high throughout platform and analyzing the sequences through an in-house pipeline, to quickly identify any potential variants of concerns. This pipeline can upload sequences directly onto the GISAID databases for sequence dissemination. The proposed work is highly significant because it will address important epidemiological question of SARS-CoV-2 prevalence along with devising strategies to minimize the viral spread. These questions include, but not limited to i) identifying variants associated with specific race/ethnic, age or gender groups; ii) variants associated with severe or critical cases of COVID-19; iii) dynamics of SARS-CoV-2 variants changeover during the study time period, and iv) whether vaccinated individuals get infected with any particular variants of SARS-CoV-2. Overall, this proposal is highly suitable for the Notice of Special Interest (NOSI): Urgent Competitive Revisions to IDeA and NARCH Programs for SARS-CoV-2 Surveillance Studies (NOT-GM-22-026).