The incidence and severity of COVID-19 infections have been disproportionately high in Native American populations. Native Americans are a high-risk group for COVID-19 because of a variety of healthcare disparities. Historically, these populations suffered excessively during previous epidemics in the United States (US). Several epidemics occurred when disease-naïve indigenous peoples were exposed to European settlers with herd immunity. Native American populations had four times higher mortality in the 1918 Spanish flu epidemic. Deaths from H1N1 infections were higher in Native Americans and most cases and deaths from the Hantavirus pulmonary syndrome (HPS) occurred in Native Americans. Other infectious diseases, including HIV, hepatitis A and hepatitis C are more also common. Diabetes, alcoholism and cardiovascular diseases, all risk factors for severity and mortality in COVID-19 infection, are also more common in this group. Addressing the root causes of enhanced risk in Native American populations will improve outcomes from COVID-19 and future pandemics.

Declaration of Competing Interest The authors have no conflicts of interest to declare.