FIGURE 1.

Schematic model of the gut-lung interaction in mild and severe COVID-19. The pulmonary immune responses in mild case were characterized by low numbers of infiltrating neutrophil and proinflammatory macrophages, along with a controlled level of proinflammatory cytokine secretion. While the predominant pulmonary immunopathology in severe COVID-19 is associated with significantly impaired interferon (IFN) responses, increased infiltration of neutrophils and proinflammatory macrophages, impaired antigen-presenting cells, reduction and functional exhaustion of cytotoxic T lymphocytes and exacerbated cytokine secretion. The intestine and lung communication enables trafficking of the immune cells and microbial metabolites along the gut-lung axis. The beneficial commensal bacteria and microbial metabolites, including short-chain fatty acids (SCFAs) and desaminotyrosine (DAT), may promote the antiviral innate immune responses and alleviate the immunopathogenic activities. Whereas the disorders of intestinal microecology may contribute to the pulmonary disease deterioration via bacteremia and the enrichment and spreading of the proinflammatory immune responses, in which the infected gut may be one of the origins of cytokine production.