Renin-Angiotensin-Aldosterone-System Blocking Drugs in Patients with SARS-CoV-2 - Systematic Review and Meta-Analysis

Background and Purpose: COVID-19 patients treated with RAAS blockers are among the patients at highest risk of poor outcome. ACE2 is the functional receptor for SARS-CoV-2. Animal studies suggest that RAAS blockers might increase the expression of ACE2 and potentially increase the risk of SARS-Cov-2 infection. Experimental Approach and Key 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 results from 16 studies in 22,333 COVID-19 patients showed that COVID-19 related server adverse clinical outcomes (admission to ICU, need for assisted ventilation or death) were reduced by 26% when using RAAS blocking agents (OR=0.74, p=0.04). Pooled results from 10 studies in 11,514 COVID-19 patients showed that RAAS blockede reduces all-cause mortality by 41% (OR=0.59, p=0.01). Conclusion and Implications: Given the weak evidence coming from animal studies and the clear beneficial data of ACE inhibition in non-COVID-19 patients and the promising data in COVID-19 patients, the use of RAAS blocking agents in patients with SARS-CoV-2 infection is justified and should be maintained. Further clinical studies analysing ARBs and ACE inhibitors separately in COVID-19 patients are needed.