How is the pathobiology of lung injury related to ACE1/ACE2
imbalance counteracted?
The data described above leads us to propose a model for pulmonary
pathology based on imbalance in RAS signaling that influences multiple
cell types (Figure 4 ) and has feedback loops that amplify
pathobiology. Most COVID-19 patients suffer minor illness and avoid
severe tissue injury. We propose that this occurs via an effective
adaptive immune response that eliminates infection and prevents the
damage induced by the RAS pathway and associated feedback mechanisms. By
contrast, patients with underlying pathologies suffer more severe
disease because of amplified RAS-driven mechanisms. These mechanisms
cause acute injury that exceed the capacity of the protective immune
response. The damaging effects of the virus via RAS/Ang II are thus
competing with the effectiveness of the immune response (Figure
4 ).