Project Summary: To date (3/23/21), Alaska has suffered over 58,000 cases of COVID-19, 1,318 hospitalizations, and 306 deaths. Alaska is a designated Primary Care Health Professional Shortage Area. Likely driven by health disparities, the COVID-19 fatality rate among American Indian/Alaska Native (AI/AN) residents of Alaska is nearly two times higher than the population of Alaska as a whole (71 v. 47 per 100,000; Alaska DHSS Bull. 1/29/21), a pattern observed in AI/AN population nationwide (CDC MMWR 12/11/20). Even with these challenges, Alaska has one of the lowest COVID-19 hospitalization and fatality rates overall, and one of the highest rates of COVID-19 vaccination. Sequencing of SARS-CoV-2 genomes has emerged as the key technology for analyzing spread of SARS-CoV-2 lineages, including detection of VOC that may cause more rapid spread, more severe disease, or reduce vaccine efficacy. Importantly, through early capacity-building by the Alaska DHSS Public Health Lab (PHL), in partnership with the University of Alaska and Alaska INBRE, over 500 SARS-CoV-2 genomes have been sequenced and released (GISAID), including recent cases of B.1.1.7, B.1.429, and P.1 variants of concern (VOC). Thus, it is important to understand the geographical and temporal spread of SARS-CoV-2 lineages in the state, and specifically in the AI/AN population. In response to this NIGMS NOSI, the Alaska INBRE (IDeA) program is proposing to extend the genomic surveillance for SARS-CoV-2 lineages and variants in Alaska, with a team of University of Alaska researchers (at UA-Fairbanks and UA-Anchorage), in collaboration with the Southcentral Foundation (SCF) and Alaska Native Medical Center (ANMC) AI/AN health networks, and support from other partners including the Alaska DHSS PHL and CDC Arctic Investigations. The project goals are (1) Prospective genomic sequencing of VOC and VOI in Alaska and comparison to other regions; (2) Prospective genomic sequencing of VOC/VOI in AI/AN health networks to understand COVID-19 disparities; and (3) Geographic and temporal analysis of SARS-CoV-2 in Alaska to inform epidemiological understanding. We will leverage both short-read (Illumina) and long-read (Nanopore) sequencing platforms, and bioinformatics expertise built by Alaska INBRE, to analyze SARS-CoV-2 genomes with samples provided by Alaska DHSS/PHL, and specifically in AI/AN (SCF and ANMC served) populations. Data will be released for meta-analyses to provide genomics perspective to epidemic tracing, understanding of spread of novel lineages, and impact of health disparities.