Hypertension. 2020 Sep 1. doi: 10.1161/HYPERTENSIONAHA.120.15989. Online ahead of print.
The viral spike (S) coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human angiotensin-converting enzyme2 (ACE2) cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for Coronavirus -19 (COVID-19) in patients taking angiotensin-converting enzyme inhibitors (ACEI)/ angiotensin II type 1 receptor antagonists (ARBs). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization data-base of COVID-19 publications and ClinicalTrials.gov through Jun 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. After pooling the adjusted odds ratios (aOR) from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACEi (aOR, 0.95; 95% CI, 0.86-1.05) or ARBs (aOR, 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)-i.e.: the use of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (< 60 years-old). The use of ACEi might not increase the susceptibility of SARS-CoV-2 infection, severity of disease and mortality in case-population and cohort studies. Additionally, we found for the first time that the use of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in younger subjects; without obvious effects on COVID-19 outcomes.