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

Abstract

Purpose: 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.Materials and Methods: 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.Result: Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR = 1.16 95% CI 0.94–1.44, p = 0.15, I2 = 93.2%) or severity (OR = 1.18, 95% CI 0.94–1.48, p = 0.15, I2 = 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.Conclusion: We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.

Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

“…Our results are in the line with the results of multiple published studies that reported that the use of RAAS inhibitors is not associated with increased short-term mortality in COVID-19 patients [17,18]. Our results that suggested a protective effect of ACEIs and ARBs are also consistent with the results of a growing number of studies that associated their use in COVID-19 patients a lower risk of mortality [19][20][21][22].…”

The effect of renin–angiotensin–aldosterone system inhibitors in patients with hypertension and COVID-19: A meta-analysis of randomized controlled trials and propensity score-matched studies

“…Our results are generally consistent with previous meta-analyses [42] , [43] , [44] , [45] , [46] of observational studies that the use of ACEIs/ARBs appears to have no significant effect on mortality or disease severity in patients with COVID-19. However, because a substantial proportion of the trials included in previous meta-analyses did not match for confounders, the crude OR may not accurately reflect the association between the use of RAAS inhibitors and COVID-19 clinical outcomes.…”

Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression

“…As of 28 December 2021 the Covid-19 pandemic has affected >281 million individuals and has led to >5.4 million global deaths (5). Even though many treatments have been proposed to combat COVID-19, there is currently no uniformly successful therapy (6)(7)(8)(9)(10)(11). Although it is a widespread disease affecting multiple systems, obesity has been identified as one of the major comorbid factors in patients suffering from COVID-19 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21).…”