Association of renin‐angiotensin‐aldosterone system inhibitors with mortality and testing positive of COVID‐19: Meta‐analysis

Abstract

Some have hypothesized that the use of angiotensin‐converting enzyme inhibitors (ACEI) and angiotensin‐receptor blockers (ARB) may modify susceptibility to coronavirus disease‐2019 (COVID‐19) in humans. Thus, we conducted two meta‐analyses to investigate the effect of ACEI and ARB on mortality and susceptibility to COVID‐19. Pubmed and EMBASE were searched through June 2020 to identify clinical trials that investigated the testing positive and in‐hospital mortality rates for COVID‐19 for those who were treated with ACEI and/or ARB and for those who were not treated with ACEI or ARB. The first analysis investigated the testing positive rate of COVID‐19. The second analysis investigated the in‐hospital mortality rate for patients with COVID‐19. Three eligible studies for the first analysis and 14 eligible studies for the second analysis were identified. The first analysis demonstrated that the use of ACEI or ARB did not affect the testing positive rates (odds ratio [OR] [confidence interval [CI]] = 0.96 [0.88–1.04]; p = .69, OR [CI] = 0.99 [0.91–1.08]; p = 0.35, respectively). The second analysis showed that the use of ACEI and/or ARB did not affect in‐hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64–1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in‐hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49‐0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID‐19 nor with mortality of COVID‐19 patients.

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019

“…[6][7][8] Others concluded that prior ACEi/ARB use reduced the risk of mortality and ICU admission, and decreased length of stay. [9][10][11][12][13][14] There is theoretical basis for both deleterious and protective effects of these agents in SARS-CoV-2 infection. 22 Notably however, there is no substantial clinical evidence that ACEi/ARB use worsens outcomes in COVID-19 when compared to appropriately matched controls.…”

“…Broadly these suggest that antecedent ACEi/ARB therapy is not associated with worsened outcomes in COVID-19, and that their use might confer certain protective benefits. [6][7][8][9][10][11][12][13][14] The impact of ACEi/ARB provision during acute COVID-19 illness has been inadequately examined. To date few studies have attempted to address this question.…”

Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on Testis

“…Since both ACE-2 as well as TMPRSS2 have been shown to be expressed in testis tissue, via single-cell and single-nucleus RNA-seq studies, we believe the high androgen environment of the testes will allow for viral entry [ 16 ]. In addition, multiple studies have reported that the use of renin-angiotensin system inhibitors has neither been shown to confer any protective effects, nor impact testing positive rates or mortality [ 17 18 19 ]. Additionally, it has been shown that viruses, such as human immunodeficiency virus, hepatitis B virus, and mumps, can cross the blood-testis barrier and cause viral orchitis resulting in infertility and cancer [ 20 ].…”

COVID-19 and male fertility: Taking stock of one year after the outbreak began

“…In patients with SARS-cov2, the use of inhibitors of the renin angiotensin system unfortunately does not confer protective effects on the testis in terms of cell mortality, probably not even with regard to spermatozoa (33). The studies analyzed, although of high quality, have some limitations.…”