@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer My thinking is it has to do with reduced tolerance for perturbations in renin-angiotensin system (RAS) with age. SARS uses ACE2 and turns down its expression, effectively increasing angiotensin II production. 1/6
@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer AngII is a major end product of the RAS system and is the root of many cardiovascular problems that arise with age - increases BP, vasoconstrictor, arterial thickening, cardiac hypertrophy, among others (all the things that often kill middle age and older guys). 2/6
@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer In presence of SARS spike gp, where vascular permeability becomes a big problem, increases in blood pressure and other AngII related downstream effects would be very likely to exacerbate vascular permeability - synergistically impacting acute respiratory failure. 3/6
@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer Add to this reduced tolerance with age for cardiac perturbations and blood pressure increase-as may often be the case, particularly older men - my best guess is children would fare better tolerating the physiological CV effects that would be expected to occur with SARS. 4/6
@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer Previous work shows that blocking AngII receptor when in presence of excess AngII due to SARS spike gp reduced vascular permeability and overall reduced lung injury - even when SARS spike was given IP. 5/6
@GlobalGutHealth @BogochIsaac @AndrewPaviaMD @florian_krammer So I think we cannot discount that ACE2 being a key receptor for SARS may have a very important role in the age distribution of severe disease with this virus - with kids doing best and older men worst. 6/6
