Fig. 2: Hypothetical mechanisms involved in early-phase COVID-19 pneumonia, as discussed in this review.

The principal steps include 1. Viral infection of AECII, 2. activation of the STAT3 pathway in AECII, 3. Abnormal STAT3-mediated cross-talk between infected AECII and noninfected endothelial cells, 4. increased expression of PD-L1 (endothelial cells and macrophages) inducing checkpoint immune inhibition of adaptive immune responses, 5. Endothelial hyper-expression of IDO inducing dilation and relaxation of pulmonary vessels, and 6. Diffusion–perfusion mismatch, shunting, pathophysiological changes, absence of alveolar collapse, vasoplegia, and “happy hypoxia”.