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Their use in the setting of COVID\u201019 has been heavily debated due to potential interactions with ACE2, an enzyme that links the pro\u2010inflammatory and anti\u2010inflammatory arms of the renin angiotensin system, but also the entryway by which severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102) invades cells. ACE2 expression is altered by age, hypertension, diabetes, and the virus itself. This study integrated available information about the renin angiotensin aldosterone system (RAAS) and effects of SARS\u2010CoV\u20102 and its comorbidities on ACE2 into a mechanistic mathematical model and aimed to quantitatively predict effects of ACEi\/ARBs on the RAAS pro\u2010inflammatory\/anti\u2010inflammatory balance. RAAS blockade prior to SARS\u2010CoV\u20102 infection is predicted to increase the mas\u2010AT1 receptor occupancy ratio up to 20\u2010fold, indicating that in patients already taking an ACEi\/ARB before infection, the anti\u2010inflammatory arm is already elevated while the pro\u2010inflammatory arm is suppressed. Predicted pro\u2010inflammatory shifts in the mas\u2010AT1 ratio due to ACE2 downregulation by SARS\u2010CoV\u20102 were small relative to anti\u2010inflammatory shifts induced by ACEi\/ARB. Predicted effects of changes in ACE2 expression with comorbidities of diabetes, hypertension, or aging on mas\u2010AT1 occupancy ratio were also relatively small. Last, predicted changes in the angiotensin (Ang(1\u20107)) production rate with ACEi\/ARB therapy, comorbidities, or infection were all small relative to exogenous Ang(1\u20107) infusion rates shown experimentally to protect against acute lung injury, suggesting that any changes in the ACE2\u2010Ang(1\u20107)\u2010mas arm may not be large enough to play a major role in COVID\u201019 pathophysiology.<\/jats:p>","DOI":"10.1002\/cpt.2177","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T21:42:06Z","timestamp":1611870126000},"page":"1092-1103","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["RAAS Blockade and COVID\u201019: Mechanistic Modeling of Mas and AT1 Receptor Occupancy as Indicators of Pro\u2010Inflammatory and Anti\u2010Inflammatory Balance"],"prefix":"10.1111","volume":"109","author":[{"given":"Karen","family":"Melissa 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