BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and 
angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) 
susceptibility, severity, and treatment is unclear.
PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either 
increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
infection or is associated with worse COVID-19 disease outcomes, and to assess 
the efficacy of these medications for COVID-19 treatment.
DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 
2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World 
Health Organization database of COVID-19 publications and medRxiv.org through 17 
April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing 
surveillance.
STUDY SELECTION: Observational studies and trials in adults that examined 
associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and 
COVID-19 disease severity and mortality.
DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, 
independent evaluation by 2 reviewers of study quality, and collective 
assessment of certainty of evidence.
DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was 
not associated with a higher likelihood of receiving a positive SARS-CoV-2 test 
result, and 1 case-control study found no association with COVID-19 illness in a 
large community (moderate-certainty evidence). Fourteen observational studies, 
involving a total of 23 565 adults with COVID-19, showed consistent evidence 
that neither medication was associated with more severe COVID-19 illness 
(high-certainty evidence). Four registered randomized trials plan to evaluate 
ACEIs and ARBs for treatment of COVID-19.
LIMITATION: Half the studies were small and did not adjust for important 
confounding variables.
CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not 
associated with more severe COVID-19 disease, and moderate-certainty evidence 
suggests no association between use of these medications and positive SARS-CoV-2 
test results among symptomatic patients. Whether these medications increase the 
risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment 
remains uncertain.
PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).