Trypsin may induce cytokine storm in M1 macrophages, resulting in critical coronavirus disease

Trypsin is a protease-activated receptor-2 (PAR2) activator that upregulates the interleukin (IL)-17 receptor signal in the airway epithelial cells and amplifies the inflammatory response, but does not modify the growth kinetics of the metapneumovirus. How does the coronavirus spread from cell to cell is yet an enigma. The present study analyzed the possible role of trypsin in the activation of coronavirus in vitro and in vivo. We found that the overexpression of trypsin in A549 cells upregulated IL-17 and angiotensin-converting enzyme (ACE). In the humanized transgenic mice, trypsin activated M1 macrophages. Together, our results suggested that the upregulation of trypsin may support a new pathway for coronavirus transmission in patients.