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Objective: To compare rates and risk factors of severe COVID-19-related outcomes between American Indian/Alaska Native (AI/AN) and non-Hispanic White people (NHW). Methods: Aggregate Social Vulnerability Index (SVI), COVID-19-related risk factor, hospitalization, and mortality data were obtained from 16 states for January 1, 2020-March 31, 2021. Generalized estimating equation Poisson regression models calculated age-adjusted cumulative incidences, incidence ratios (IR), and 95% confidence intervals (CI) comparing AI/AN and NHW persons by age, sex, and county-level SVI status. Results: Race data were missing for 42.7% of COVID-19 cases, 24.7% of hospitalizations, and 10.1% of deaths. Risk of AI/AN COVID-19 mortality was 2.6 times that of NHW persons (IR 2.6, 95% CI: 1.7 - 3.4); risk of COVID-19-related hospitalization among AI/AN persons was 3.5 times that of NHW (IR: 3.5, 95% CI: 2.7 - 4.3). Severe COVID-19 outcomes were significantly higher for AI/AN persons compared to NHW persons across all age and sex groups. There was no statistically significant difference in COVID-19 outcomes by SVI status. Associations between severe COVID-19 outcomes and co-morbid risk factors were inconsistent. Conclusions: Results describe increased risk of severe COVID-19 outcomes for AI/AN persons compared to NHW persons despite quality issues in public health surveillance data. Data linkages and improved ascertainment reduce race/ethnicity misclassification and improve data quality. COVID-19-related health burdens among AI/AN persons warrant improved access for AI/AN communities to medical countermeasures and healthcare resources. [ABSTRACT FROM AUTHOR]