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 ).