AGT and endothelial dysfunction: Given that hACE2 is known to attenuate acute lung injury in mouse models of SARS-CoV-1 mediated ARDS (49, 61), reduced local hACE2 availability and subsequent hyperactivation of angiotensin II–mediated (ATII-mediated) signaling may represent a possible mechanism of spike protein–induced endothelial dysfunction and aggravation of pulmonary damage (51).