Mortality and Severity in COVID-19 Patients on ACEIs and ARBs-A Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

The primary objective of this systematic review is to assess association of mortality in COVID-19 patients on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin-II receptor blockers (ARBs). A secondary objective is to assess associations with higher severity of the disease in COVID-19 patients. We searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for longitudinal studies globally reporting mortality and severity published before January 18th, 2021. Meta-analyses were performed using 53 studies for mortality outcome and 43 for the severity outcome. Mantel-Haenszel odds ratios were generated to describe overall effect size using random effect models. To account for between study results variations, multivariate meta-regression was performed with preselected covariates using maximum likelihood method for both the mortality and severity models. Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR = 1.16 95% CI 0.94-1.44, = 0.15, = 93.2%) or severity (OR = 1.18, 95% CI 0.94-1.48, = 0.15, = 91.1%) in comparison to not being on ACEIs/ARBs in COVID-19 positive patients. Multivariate meta-regression for the mortality model demonstrated that 36% of between study variations could be explained by differences in age, gender, and proportion of heart diseases in the study samples. Multivariate meta-regression for the severity model demonstrated that 8% of between study variations could be explained by differences in age, proportion of diabetes, heart disease and study country in the study samples. We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.