In a kind of positive feedback loop, the ADAM17-mediated shedding activity appears to be enhanced by the binding of the viral spike protein to ACE2 [23,62,63], and to be stimulated by AngII [42] and the pro-inflammatory cytokines interleukin (IL)-1β and TNF-α [64], whose secretion is elevated in COVID-19 patients. Here, ACE2 is linked to COVID-19.