Ecological Analysis of the Influence of ACEIs and ARBs on the COVID-19 Prevalence and Death from COVID-19

Abstract

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) have been an arguable risk factor for COVID-19 diseases because they could upregulate Angiotensin Converting Enzyme-2 (ACE2) expression, facilitating SARS-CoV2 entry to the lungs. Several retrospective clinical studies, however, found no such effect. Here, we explore how the use of ACEIs and ARBs links to COVID-19 across all countries of the world. Methods: Data on the availability of ACEIs and ARBs for 200 countries and on the number of cases and number of deaths per country by 28 December 2020 were extracted from WHO and Worldometer website, respectively. Data on life expectancy at age 65 years as a measure of ageing were from WHO and on Gross Domestic Product Per Capita (GDP PPP) and the percentage of urbanization were from the World Bank. Excel and SPSS v 26 software were used for statistical analyses. Results: In linear regression and logistic conditional regression analysis, GDP correlates with COVID-19 prevalence (rho = 0.66, p > 0.001) and deaths from COVID-19 (rho = 0.55, p < 0.001) while urbanization and life expectancy do not when GDP influence is controlled for. After statistically removing the effects of GDP on the prevalence and mortality from COVID-19, we found that countries without ACEI and ARB availability had lower COVID-19 cases and deaths (p < 0.02). Conclusions: Our study based on the global data contradicts findings of most published clinical studies at regional levels. We found that GDP positively correlates with prevalence of and mortality related to COVID-19. ACEI and ARB use increases COVID-19 infectivity and mortality.

Keywords

COVID-19, RAAS Inhibitors, Ecological Analysis, ACEIs, ARBs