Enhanced ACE1/ACE2 imbalance in comorbidities that influence COVID-19 morbidity and mortality
Why do some patients, with comorbidities have increased susceptibility to morbidity and mortality from COVID-19? Our model for pulmonary and cardiac injury implies a role for crosstalk between ACE2-expressing cells infected by SARS viruses and other cell types, especially inflammatory cells (e.g., macrophages and neutrophils) and fibroblasts. In patients with underlying disease, one or more of these cell types may be dysfunctional. Superimposed SARS-CoV-2 infection further amplifies ANG II signaling (which promotes injury) and suppresses ANG (1-7) signaling (which opposes injurious effects), thus increasing pathobiology. Multiple clinical conditions may be associated with elevated vulnerability to COVID-19. Examples include:
Chronic Lung Injury/Disease . Lung injury (e.g., from fibrotic disease, smoking or radiation) is associated with increased local inflammatory signaling, predisposing the epithelium to ANG II-promoted injury. In these settings, epithelial cells and fibroblasts can have elevated a net increase in pro-inflammatory ANG-mediated responses. The addition of SARS-CoV-2 further increases this imbalance, thereby enhancing lung injury.
Therefore, the ACE1/ACE imbalance model for SARS-CoV-2 pathobiology can help explain how/why patients with certain underlying conditions/comorbidities are at greater risk if infected with SARS-CoV-2/COVID-19. Elderly individuals are at particular risk, since many of the comorbidities are age-associated. Those with health conditions such as immune deficiencies, diabetes, or cardiac disease will likely be at greater risk for more severe COVID-19 infections and ACE1/ANGII-mediated pathology. By contrast, children (who lack comorbidities associated with ACE1/ACE2 imbalance) are predicted to have less morbidity and mortality from COVID-19.