COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Etiology Chan CK, Huang YS, Liao HW, et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis. Hypertension. 2020 Nov;76(5):1563-1571. doi: 10.1161/HYPERTENSIONAHA.120.15989. Epub 2020 Sep 1.

The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.

Discipline / Specialty Area Score
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Family Medicine (FM)/General Practice (GP)
Intensivist/Critical Care
Infectious Disease
Emergency Medicine
Comments from MORE raters

Emergency Medicine rater

These are interesting results; however, they do not directly impact the practice of emergency medicine.

Family Medicine (FM)/General Practice (GP) rater

This is a very interesting systematic review of retrospective and prospective cohort studies. The bias dependency of the meta-analysis also results from the design of the studies. So far, this year their have been a number of studies on the use of ACE inhibitors and ARB in connection with COVID-19 infections. At least one or the other of these studies should have become known to the general practitioners. However, the aspect that ARB could increase the risk of severe COVID-19 courses, especially in younger people, is likely to be completely new. However, since this is only the result of cohorts, further studies will have to be awaited.