Renin-angiotensin-aldosterone system blocking drugs in patients with SARS-COV-2: Systematic review and meta-analysis

Background: COVID-19 patients requiring treatment with blockers of the reninangiotensin- aldosterone system (RAAS) are at highest risk of developing pneumonia and dying ACE2 is the functional receptor for SARS-CoV-2 Animal studies suggest that RAAS blocking agents might increase the expression of ACE2 and hence potentially increase the risk of SARS-Cov-2 infection Methods: We conducted a systematic review and meta-analysis of published studies on the association of RASS blocking agents with lung disease related outcomes Results: The effect of ACE inhibitor treatment on the incidence of pneumonia in non-COVID-19 patients was analyzed in 25 studies (330,780 patients) ACE inhibitor use was associated with a 27% reduction of pneumonia risk (OR: 0 73, p<0 001) Pneumonia related death cases in ACE inhibitor treated non-COVID-19 patients were reduced by 27% (OR: 0 73, p=0 004) ARB treatment was analyzed in 10 studies (275,621 non- COVID-19 patients) The risk of pneumonia was not different between patients who did or did not use ARBs Pooled result from 13 studies (27,704 COVID-19 patients) showed that COVID-19 related severe adverse clinical outcomes were not different between patients who did or did not use RAAS blocking agents (OR: 0 87, p=0 28) All-cause mortality risk in COVID-19 patients was reduced by 27% (p=0 04) Conclusions: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the limited but promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARSCoV- 2 infection is justified Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed