Renin-Angiotensin System Inhibitors and COVID-19: a Systematic Review and Meta-Analysis. Evidence for Significant Geographical Disparities.

PURPOSE OF REVIEW: While the COVID-19 pandemic is constantly evolving, it remains unclear whether the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) affects the clinical course of SARS-CoV-2 infection. For this meta-analysis, PubMed, CENTRAL, and grey literature were searched from their inception to 19 May 2020 for randomized, controlled trials or observational studies that evaluate the association between the use of either ACE inhibitors or ARBs and the risk for major clinical endpoints (infection, hospitalization, admission to ICU, death) in adult patients during the COVID-19 pandemic. In addition, a subgroup geographical analysis of outcomes was performed. Studies including less than 100 subjects were excluded from our analysis. RECENT FINDINGS: In total, 25 observational studies were included. ACE inhibitors and ARBs were not associated with increased odds for SARS-CoV-2 infection, admission to hospital, severe or critical illness, admission to ICU, and SARS-CoV-2-related death. In Asian countries, the use of ACE inhibitors/ARBs decreased the odds for severe or critical illness and death (OR = 0.37, 95% CI 0.16-0.89, I2 = 83%, and OR = 0.62, 95% CI 0.39-0.99, I2 = 0%, respectively), whereas they increased the odds for ICU admission in North America and death in Europe (OR = 1.75, 95% CI 1.37-2.23, I2 = 0%, and OR = 1.68, 95% CI 1.05-2.70, I2 = 82%, respectively). ACE inhibitors might be marginally protective regarding SARS-CoV-2-related death compared with ARBs (OR = 0.86, 95% CI 0.74-1.00, I2 = 0%). Randomized controlled trials are needed to confirm the aforementioned associations between ACE inhibitors, ARBs, and SARS-CoV-2.