Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

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ABSTRACT

Background:
The role of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear.

Purpose:
To evaluate, on an ongoing basis, whether ACEI or ARB use increases the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and evaluate the effectiveness of these medications for the treatment of COVID-19.

Data sources:
MEDLINE (Ovid) and the Cochrane Database of Systematic Reviews from 2003 to May 4, 2020, with planned surveillance ongoing for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org as of April 17, 2020; and ClinicalTrials.gov through April 24, 2020, with planned surveillance ongoing.

Study selection:
Observational studies and trials in adults that examined the associations and effects of ACEIs or ARBs on the risk of SARS-CoV-2 infection and COVID-19 disease severity and mortality.

Data extraction:
Single reviewer abstraction confirmed by another reviewer, independent assessment by 2 reviewers of study quality, and collective assessment of the certainty of the evidence.

Data synthesis:

• Two retrospective cohort studies found that ACEI and ARB use was not associated with an increased likelihood of receiving a positive SARS-CoV-2 test result.
• 1 case-control study found no association with COVID-19 disease in a large community (moderate-certainty evidence).
• Fourteen observational studies, involving a total of 23 adults with COVID-565, showed consistent evidence that none of the medications was associated with more severe COVID-19 disease (high-certainty evidence).
• Four registered randomized trials plan to evaluate ACEIs and ARBs for the treatment of COVID-19.

Limitation:
Half of the studies were small and did not adjust for important confounding variables.

Conclusion:
High-certainty evidence suggests that use of ACEIs or ARBs is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests that there is no association between use of these medications and positive test results. SARS-CoV-2 among symptomatic patients. It is not yet known whether these medications increase the risk of mild or asymptomatic disease or are beneficial in treating COVID-19.