INTRODUCTION: The use of renin-angiotensin system (RAS) inhibitors, including 
angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor 
blockers (ARBs), was alleged to cause a more severe course of novel coronavirus 
disease 2019 (COVID-19).
METHODS: We systematically reviewed the published studies to assess the 
association of RAS inhibitors with mortality as well as disease severity in 
COVID-19 patients. A systematic literature search was performed to retrieve 
relevant original studies investigating mortality and severity (severe/critical 
disease) in COVID-19 patients with and without exposure to RAS inhibitors.
RESULTS: A total of 59 original studies were included for qualitative synthesis. 
Twenty-four studies that reported adjusted effect sizes (24 studies reported 
mortality outcomes and 16 studies reported disease severity outcomes), conducted 
in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects 
models to estimate overall risk. Quality assessment of studies revealed that 
most of the studies included were of fair quality. The use of an ACEI/ARB in 
COVID-19 patients was significantly associated with lower odds (odds ratio 
[OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard 
(hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared 
with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly 
associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard 
(HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease 
compared with non-use of an ACEI/ARB.
DISCUSSION: Since there was no increased risk of harm, the use of RAS inhibitors 
for hypertension and other established clinical indications can be maintained in 
COVID-19 patients.