Abstract
Introduction: Sex differences in COVID-19 outcomes are well-known and have been ascribed to numerous factors including age-dependent sex hormones. We hypothesize that the protective effect of female sex in hospitalized COVID-19 patients attenuates with age. Methods: We retrospectively analyzed patients who were hospitalized for COVID-19 infection at three hospitals of the Rush University System for Health (RUSH) (Chicago, IL) between March to December 2020. The primary endpoints were in-hospital mortality and major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac arrest, acute heart failure, and stroke. Stratified logistic regression was performed to estimate the odds ratios of these endpoints in male compared to female patients by age group (<45, 45-55, 55-65, 65-75, and ≥75 years). Results: Of 1705 patients (age 58.1±16.9 years, 54.3% male, 24.6% White) who were hospitalized for COVID-19 infection, 179 (10.5%) patients experienced in-hospital mortality and 290 (17.0%) patients experienced MACE, respectively. The incidence of these outcomes progressively increased with age in both sexes. In patients <45 years of age, there was a trend towards increased risk for in-hospital mortality (aOR 4.47; 95% CI: 0.54 - 42.38) and MACE (aOR 2.43; 95% CI: 0.97 - 6.10) in men compared to women. However, this trend attenuated with increasing age strata and there was a slight decrease in risk for in-hospital mortality (aOR 0.79; 95% CI: 0.39 - 1.58) and MACE (aOR 0.70; 95% CI: 0.38 - 1.28) among middle-aged (55-65 years of age) men compared to women. Conclusions: In this multi-hospital registry of COVID-19 patients, there was a reverse J-shaped trend in odds of in-hospital mortality and MACE in men compared to women. Female sex appeared to be an independent protective factor for adverse hospital outcomes among patients <55 years of age but not among older patients, suggesting a protective role of premenopausal sex hormones.
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