Abstract
Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.
Highlights
Coronavirus disease 19 (COVID-19) emerged in December 2019 as a novel viral pneumonia, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [1]
As for out outcome indicators, 53 (44.5%) patients developed acute respiratory distress syndrome (ARDS) with a higher incidence in males compared to females
A significant male-female difference in the severity of COVID-19 cases has been reported in medical literature [1,2,3,4,5,6]
Summary
Coronavirus disease 19 (COVID-19) emerged in December 2019 as a novel viral pneumonia, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [1]. Epidemiological studies have shown that clinical manifestations of SARS-CoV-2 include asymptomatic infection, bilateral pneumoniae, acute respiratory distress syndrome (ARDS), and death [1]. Studies worldwide have shown that sex is an important risk factor in COVID-19 outcomes [1,2,3,4]. Klein and colleagues reported a significant male-female difference in COVID-19 cases, hospitalizations, and deaths [5]. Men were more likely to require intensive care than women, and had a higher mortality rate [6]. Sex disaggregated data from 190 countries confirmed a greater mortality rate in men, especially if over 50 years of age [7]
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