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

Romil Singh,Sohini Anand,Vikas Bansal,Fnu Ayesha,Janaki Makadia,Prithwish Ghosh,Mack Sheraton,Kiran S Mahapure,Abhishek Bhurwal,Abhishek Bhurwal,Hira Khan,Sawai Singh Rathore,Aysun Tekin,Rahul Kashyap,Ishita Mehra

doi:10.3389/fmed.2021.703661

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.

Highlights

SARS-CoV-2 originated in Wuhan, China, in December 2019 and has spread to every major country in the world and was subsequently declared a pandemic on March 11, 2020 [1]
Result: Our findings showed that the use of Angiotensin-converting-enzyme inhibitors (ACEIs)/Angiotensin-II receptor blockers (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
We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs

Summary

Introduction

SARS-CoV-2 originated in Wuhan, China, in December 2019 and has spread to every major country in the world and was subsequently declared a pandemic on March 11, 2020 [1]. As of April 29th, 2021, there were 150,088,112 positive patients worldwide; and 3,161,337 of these patients were reported to be deceased because of SARS-CoV-2 [2]. The case fatality rate of SARS-CoV-2 in the U.S is 1.8% as per COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University [2]. The SARS-CoV-2 disease varies from mild to fulminant in reference to several risk variables contributing to a poor prognosis [3,4,5]. Thorough awareness of the risks, pathogenesis, and predisposing factors together with the important aspects in the diagnosis is of paramount importance in order to direct decision-making for acute care and mitigate mortality of COVID-19 [15,16,17,18]

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