Figure 2.

The association between cytokine release syndrome (CRS) and renin-angiotensin system (RAS). ACE2 is a key anti-regulatory enzyme that converts Ang II to Ang1-7. Following viral complex endocytosis, ACE2 is downregulated and lost from the surface of the host cell, resulting in angiotensin II accumulation. Through the AT1R-metalloprotease 17 (ADAM17) axis, Ang II constricts blood vessels and acts as a proinflammatory cytokine. The membrane form of IL-6Ra can be cleaved by ADAM17, resulting in soluble IL-6R that binds to IL-6 and activates STAT3. This trans-signalling causes CRS, which results in the production of several proinflammatory cytokines and chemokines, including increased IL-6. As a result, the feedback loop of the IL-6 amplifier (IL-6 Amp) may act as a switch to launch “cytokine storms.” This figure is reproduced from Li et al. [26] after permission from Springer Nature (license no. 5445930573563).