Figure 1 . The RAAS controls blood pressure through the systemic secretion of renin from juxtaglomerular cells in the kidneys when renal i.e. blood pressure and/or salt intake are diminished. Renin, then converts angiotensinogen, which is released from the liver, into Ang I (1-10) which is then processed by ACE into Ang II (1-8). This compound stimulates the secretion of aldosterone (mineralocorticoid) from the adrenal cortex leading to sodium retention and acts mainly on AT1 receptors leading to vasoconstriction. ACE2 negatively regulates the RAAS by converting Ang II (1-8) into Ang (1-7) which acts on Mas receptors leading to vasodilation. ACE inhibitors, ARBs and MCRA are widely used as anti-hypertensive drugs and for treatment of heart and renal failure. ACE2 is expressed in human lungs and COVID-19 spike (S) protein seems to use it as a cellular entry receptor. It is still a research question whether age and the use of ACE inhibitors and/or ARBs could impact on ACE2 expression and consequently affect the infection pattern of COVID-19. Another aspect is that ARBs might stabilize the ACE2-AT1 receptor interaction and might prevent viral S protein-ACE2 interaction and internalization, see also supplementary material: Molecular Background. Clinical data indicated that SARS-CoV-2 infection related myocarditis and heart failure may negatively influence outcome of SARS- CoV-2 pneumonia. ACE inhibitor treatment reduces the risk of pneumonia and
pneumonia related mortality, whereas ARBs do not reduce the risk of pneumonia in non-COVID-19 patients. Treatment with RASS blocking drugs reduces severe adverse clinical outcomes and all-cause mortality in COVID-19 patients.
RAAS = Renin angiotensin aldosterone system, Ang = Angiotensin, ACE = Angiotensin converting enzyme, AT1 receptors = Angiotensin 1 receptors, ARBs = Angiotensin receptor blockers, MCRA = Mineralocorticoid receptor antagonists, COVID-19 = Coronavirus disease 19.