ARBs and ACE Inhibitors Are Associated With Improved Outcomes in Males Hospitalized With COVID-19
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Crisis Management, Pharmacology, 2022
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INTRODUCTION/HYPOTHESIS: SARS-CoV-2 spike protein binds and down-regulates angiotensin-converting enzyme 2 (ACE2), possibly increasing angiotensin II (pro-inflammatory). ACE2 is on the X chromosome and males account for more ICU admissions and deaths. We propose sex-differences in renin-angiotensin system (RAS) peptides contribute to sex disparity and use of ARBs or ACEi is associated with greater improvement in clinical outcomes in males than females hospitalized with COVID-19.
METHODS: ARBs CORONA I is a multisite Canadian cohort study of hospitalized COVID-19 patients. We recorded baseline characteristics, comorbidities, pre-hospital/hospital treatment with ARBs/ACEi, ICU admission, use of ventilation, vasopressors, renal replacement therapy (RRT) and mortality. We compared the effects of ARBs/ACEi versus no ARBs/ACEi in males versus females. RAS peptides (ELISAs) and proteomics (169 proteins) were measured at hospital admission (day 0) and days 2, 4, 7 and 14 (subgroup; n=46). Multivariable Cox regression determined adjusted hazard ratio for time to outcomes. Multivariable logistic regression determined adjusted odds ratio of outcomes according to sex and ARBs/ACEi treatment.
RESULTS: We included 1687 patients (02/20 to 04/21). Males had significantly greater adjusted odds of ICU admission (aOR=1.42, p=0.008), ventilation (aOR=1.45, p=0.006), and vasopressors use (aOR=1.46, p=0.005) compared to females. Among males on either ARBs or ACEi, there was significantly less ventilation (aOR=0.62, p=0.012), vasopressors (aOR=0.67, p=0.032) and RRT (aOR=0.52, p=0.041), compared to males not on ARBs/ACEi. No significant effects were observed in females with exception of significantly earlier time to discharge on ARBs/ACEi compared to females not on ARBs/ACEi (aHR=1.25, p=0.038). Angiotensin II was higher in males (median=109 pg/ml) compared to females (median=66 pg/ml) on day 7 (p=0.048), as was day 0 ACE (adjusted median difference=78.1 ng/ml, p=0.042). In longitudinal analysis, thrombospondin-1 (p=0.00025) and matrix metalloproteinase-9 (p=0.012) were significantly higher in females than males.
CONCLUSION: Males hospitalized with COVID-19 had significantly better responses to ARBs/ACEi compared to females. Sex-based dysregulation of RAS may contribute to sex-based differences in outcomes and responses to ARBs/ACEi.
Meta Tag
Content Type Presentation
Knowledge Area Pharmacology
Knowledge Area Crisis Management
Knowledge Level Intermediate
Knowledge Level Advanced
Membership Level Select
Tag Pharmacology
Tag COVID-19
Year 2022
Genevieve Droshlo
COVID-19 outcomes
sex differences
renin-angiotensin system pathway


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