• J M Carethers.
• From the, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
• J. Intern. Med. 2021 Apr 1; 289 (4): 463-473.

AbstractThe onset of human disease by infection with SARS-CoV-2 causing COVID-19 has revealed risk factors for disease severity. There are four identified factors that put one at high risk for infection and/or mortality creating a disparity: age, co-morbidities, race/ethnicity and gender. Data indicate that the older a person is, and/or the presence of obesity and diabetes, cardiovascular disease and chronic kidney disease place one at higher risk for COVID-19. In the United States, specific race/ethnicities, particularly African Americans and Native Americans, are strong COVID-19 risk components. Male gender has also emerged as a severity risk factor. For age and racial/ethnicities, the accumulation of health co-morbidities is common precipitating mechanisms. In particular, underlying socio-economic structures in the United States likely drive development of co-morbidities, putting affected populations at higher risk for severe COVID-19. Sudden cardiac death triggered by a common sodium channel variant in African Americans with COVID-19 has not been evaluated as a cause for racial disparity. There is no evidence that racial/ethnic differences for COVID-19 are caused by ABO blood groups, use of angiotensin-converting enzyme (ACE) inhibitors or from amino acid substitutions in the SARS-CoV-2 spike protein. There is growing evidence that androgen-enabled expression of ACE2 receptors and the serine protease TMPRSS2, two permissive elements engaging the SARS-CoV-2 spike protein for infection, may contribute to severe COVID-19 in men. Overall, COVID-19 has generated disparities for who is infected and the severity of that infection. Understanding the mechanisms for the disparity will help nullify the differences in risk for COVID-19.© 2020 The Association for the Publication of the Journal of Internal Medicine.

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