Fig. 1

Immunopathogenesis of the SARS-CoV-2. The alveolar epithelium consists of a monolayer of alveolar type I (AT1) cells and alveolar type II (AT2) cells. Under normal condition, the AT2 cells secrete surfactant covering all the lining epithelium to facilitate alveolus expansion. AT1 and AT2 are tightly connected with tight junctions, which control the transfer of ions and fluid across the epithelium. The endothelial cells of the blood capillaries are connected by intercellular junctions and control the influx of inflammatory cells and fluid into the interstitial space. SARS-CoV-2 infects AT2 cells and resident alveolar macrophages that express ACE2. This activation induces chemokine secretion that recruits inflammatory and immune cells into the infected alveoli. The increased inflammatory cells in the lung lead to secretion of large amounts of pro-inflammatory cytokines “cytokine storm” that lead to damages in the lung. The migrated neutrophils and monocytes release toxic mediators, causing endothelial and epithelial injuries. The intercellular junctions are disrupted leading to formation of gaps between the alveolar cells as well as between the endothelial cells, resulting in an increase in the permeability of the epithelial and endothelial cells. The increase in the permeability facilitates the migration of inflammatory cells and allows the influx of RBCs and fluid from the blood capillary. Large volume of fluid (alveolar edema) fills the airspace leading to a difficulty in the breathing. Also, the inflammatory reactions may lead to alveolar cell death, fibrin deposition, and hyaline membrane formation