Background The COVID-19 pandemic has highlighted health inequities among indigenous populations, with those in rural settings facing compounded barriers.Purpose To investigate morbidity and mortality experiences among hospitalized, COVID-19+ American Indian adults from rural and urban settings.Methods The described cross-sectional study used retrospective discharge data from the University of Mississippi Medical Center and Hennepin County Medical Center. Adults (≥ age 18) admitted from January 1, 2020 to August 8, 2021with a COVID-19 diagnosis and known race were included.Results A total of 3,659 inpatients met inclusion criteria. Among adults hospitalized with COVID-19 at the University of Mississippi Medical Center, American Indians (n=73) had the highest mean comorbidity risk score (11.2, SD 8.1) and unadjusted mortality rate (42%) among all races. Among adults hospitalized with COVID-19 at Hennepin County Medical Center, American Indians (n=62) had the second lowest comorbidity risk score (6.1, SD 10.7) and the lowest unadjusted mortality rate (6%). American Indian mortality disparities persisted after controlling for age, sex, and comorbidity risk.Conclusion Hospitalized American Indians from predominantly rural settings experienced significant morbidity and COVID-19 mortality disparities when compared to native persons in predominantly urban environments, or Blacks and Whites in either setting. Compounded disparities faced by rural, indigenous populations must be addressed
