Fig. 2

Mucosal immune system in the upper respiratory tract. The mucosal immune system in the airway mainly includes a ciliated epithelial cell layer in which club and goblet cells are the main mucosal secretory cells that secrete mucin and mucosal lipids. Basal cells are epithelial stem cells that renew and supplement epithelial cells. During SARS-CoV-2 invasion, T cells are activated and natural killer cells, macrophages, and neutrophils pass through the endothelial cells of the capillaries to the lamina propria to perform their immune functions. DCs secrete IL-12 to activate Th1 cells, IL-2 and IL-4 to activate Th2 cells respectively. Th1 and Th2 exhibit an antagonistic relationship. IFN-γ secreted by NK cells and Th1 cells can promote cellular antiviral response. Activated Th2 cells play a more important role in the germinal center. IL-6 mainly produced by macrophages and Th2 cells is a significant biomarker for severe COVID-19. The cilia can cross the mucosal layer to contact SARS-CoV-2, and the cilia surface can express angiotensin converting enzyme-2 and transmembrane protease serine 2; thus, they can transport SARS-CoV-2 directly. Ciliary dyneins can transfer SARS-CoV-2 to the cell surface and infect the cells through receptors on the cell surface. After infection, the PAK 1/4 pathway activates the reprogramming of cytoskeletal proteins in the microvilli, making the microvilli longer and larger. Reprogrammed microvilli can extend more viral particles to the mucus layer, which is prone to viral transmission