The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications

The pivotal link between ACE2 deficiency and SARS-CoV-2 infection: One year later

“…At the beginning of the pandemic it was assumed that a mild or moderate deficiency of ACE2 could protect from viral infection. To date, this hypothesis appears to be rejected by the evidence that symptoms, clinical presentation and outcome of COVID-19 may be consistently related to molecular changes and dysregulation of the RAAS [ 13 , 15 , 85 , 86 ]. The interaction between ACE2 and SARS-CoV-2 Spike protein induces a substantial loss of ACE2 receptor activity from the external site of the cellular membrane.…”

ACE2, the Counter-Regulatory Renin–Angiotensin System Axis and COVID-19 Severity

“…Thus, from a (patho)physiological point-of-view an increase in the membrane bound ACE2, the SARS-CoV-2 receptor, in the lungs will most likely increase susceptibility to COVID-19 [44], as it is dubious whether it will bolster the counter-regulatory RAS axis (Figure 2) [38,45].…”

“…COVID-19 [44], as it is dubious whether it will bolster the counter-regulatory RAS axis (Figure 2) [38,45].…”

“…As a result, deleterious signalling (inflammation, thrombosis and fibrosis) dominates over protective (vasodilation, vasoprotection and tissue protection) signalling in patients with severe COVID-19, which may lead to acute lung injury. Abbreviations: AT1R, angiotensin receptor type 1; AT2R, angiotensin receptor type 2[45].…”

Myocarditis, Pericarditis and Cardiomyopathy After COVID-19 Vaccination

“…The impact of the global health crisis due to the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)—the causative pathogen of the coronavirus disease 2019 (COVID-19)—has begun to alter with the timely development, approval and administration of vaccines [ 1 ]. Although SARS-CoV-2 infection primarily targets the respiratory system [ [2] , [3] , [4] , [5] , [6] ], it is now recognised that the infection and its clinical manifestations are systemic [ [7] , [8] , [9] , [10] , [11] , [12] ], and also affecting the cardiovascular system of adults and children [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] ]. Cardiac complications of variable severity with acute and long-term sequelae are now known to include acute myocardial injury, arrhythmias, vasculitis and endothelial dysfunction, thrombosis, myocardial fibrosis, and myocarditis [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] ].…”