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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: JPEN J Parenter Enteral Nutr. 2020 Nov 13;45(1):13–31. doi: 10.1002/jpen.2036

Table 2.

Proposed Mechanisms Linking Risk Factors With Severe COVID-19.

Type Risk factor Proposed mechanism References
Nonmodifiable Increased age Increased ACE2 expression, viral load, and proinflammatory immune responses 15
Male Androgens modulate TMPRSS2 gene expression TMPRSS2 primes SARS-CoV-2 spike protein 16
Modifiable Social determinants of health Disenfranchisement leads to decreased access to quality healthcare and increased exposure to unhealthy behaviors and environmental factors, leading to poorer health and increased risk factors for chronic disease and COVID-19 severity 17
Cardiometabolic Based on the CMBCD model,1 there is increased ACE2 susceptibility and loss of cardioprotection, hypercytokinemia and insulin resistance, and SARS-CoV-2 and ACE2-mediated β-cell defect 18
Immunity/chronic disease Increased endothelial dysfunction, proinflammatory state, and abnormal innate immune response 19

ACE2, angiotensin-converting enzyme 2; CMBCD, cardiometabolic-based chronic disease; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane protease, serine 2.