FIGURE 5  Immunopathological changes during different stages of COVID-19. (A) Immunological response in mild/moderate COVID-19 patients are overtly conferred by the adaptive immune cells with assistance from the innate immune system. Infected ATII cells and activated AMs produce a repertoire of cytokines and chemokines to recruit innate and adaptive immune cells and limit the viral propagation. The functional immune system thus acts in a well-coordinated manner to eliminate the virus specific ATII cells. Due to the relatively stem cell-like property of ATII cells, the eliminated cells are subsequently regenerated, thus ensuring recovery of the damaged lung tissue. (B) However, in severe/critically ill patients, an exaggerated inflammatory response is mounted by hyperactivated innate immune cells, and to a lower degree by adaptive immune cells. A hyperinflammatory state is created in the lungs which is characterized by the robust accumulation of inflammatory cells like monocytes/macrophages, dendritic cells, and neutrophils. This leads to the excessive release of cytokines and chemokines by these cells, thus inducing a vicious hyperinflammatory cycle. Damage to the lung parenchyma is inflicted by this hyperinflammatory state, along with other cytotoxic molecules like MMPs, NETs, ROS and NO. The latter two combine to form more cytotoxic peroxynitrite ions. The combined action of these events results in epithelial denudation, vascular leak, platelet and RBC infiltration, vascular edema, and hyaline membrane formation, resulting in ARDS.