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

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.

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

Background:High-quality evidence for whether the use of renin–angiotensin–aldosterone system(RAAS)in-hibitors worsens clinical outcomes for patients with coronavirus disease 2019(COVID-19)is lacking.The present study aimed to evaluate the effect of RAAS inhibitors on disease severity and mortality in patients with hyper-tension and COVID-19 using randomized controlled trials(RCTs)and propensity score-matched(PSM)studies.Methods:A literature search was conducted with PubMed,Embase,and Scopus databases from 31 December 2019 to 10 January 2022.We included RCTs and PSM studies comparing the risk of severe illness or mortality in patients with hypertension and COVID-19 treated or not treated with RAAS inhibitors.Individual trial data were combined to estimate the pooled odds ratio(OR)with a random-effects model.Results:A total of 17 studies(4 RCTs and 13 PSM studies)were included in the meta-analysis.The use of RAAS inhibitors was not associated with an increased risk of severe illness(OR=1.00,95%confidence interval[CI]:0.88–1.14,I^(2)=28%)or mortality(OR=0.96,95%CI:0.83–1.11,I^(2)=16%)for patients with hypertension and COVID-19.Furthermore,there was no significant difference in the severity of COVID-19 when patients continued or discontinued treatment with RAAS inhibitors(OR=1.01,95%CI:0.78–1.29,I^(2)=0%).Conclusions:This study suggests that there was no association between treatment with RAAS inhibitors and worsened COVID-19 disease outcomes.Our findings support the current guidelines that RAAS inhibitors should be continued in the setting of the COVID-19 pandemic.However,the benefit of RAAS inhibitor medications for COVID-19 patients should be further validated with more RCTs.