Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study

Abstract

Objective: Male sex is a determinant of severe coronavirus disease-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. Methods: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation [IMV], death, intensive care unit [ICU] admission and home discharge at day 7 [D7] or day 28 [D28]) in 2,380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). Results: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR 0.66 [0.49-0.88]), death (OR 0.49 [0.30-0.79]) and ICU admission (OR 0.57 [0.43-0.77]) at D7, but only with ICU admission (OR 0.58 [0.43-0.77]) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, CRP, AST and eGFR predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. Conclusions: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Sexual dimorphism in COVID-19: potential clinical and public health implications

“…The authors of this study concluded that diabetes might reduce the protection that women have over men in terms of susceptibility to severe COVID-19. 12 In another cohort study of people with diabetes, male sex, among other factors, such as living in residential care, was identified as a risk factor for developing fatal or critical care unit-treated COVID-19. 13 Cardiovascular disease is the leading cause of death among men and women, although epidemiological observations indicate that women have a lower risk of major adverse cardiovascular events than age-matched men and that the manifestation of cardiovascular disease in women is delayed, as cardiovascular risk increases in women predominantly after the menopause.…”

Does diabetes mellitus mitigate the gender gap in COVID-19 mortality?

“…The latest sex-disaggregated post hoc analysis of the CORONADO study published in this journal reported sex disparities in severe COVID-19 outcomes of hospitalized patients with DM. After multiple adjustments, female sex was inversely related to the primary outcome (IMV and/or death), mortality or ICU admission at day 7, and ICU admission at day 28 ( 7 ). In addition, chronic obstructive pulmonary disease (COPD) predicted death in women only.…”

Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men

“…Interestingly, premorbid total testosterone concentrations was a predictor of COVID-19 mortality risk. Lower testosterone concentrations in men are associated with higher risk of obesity and type 2 diabetes and with the presence of medical comorbidities, all of which are risk factors for poorer outcomes in COVID-19 ( 5 , 6 , 7 , 8 , 9 ). The lower limb of the U-shaped relationship between serum total testosterone and COVID-19 mortality risk in minimally adjusted analysis may reflect the association of lower serum testosterone with adverse sociodemographic, lifestyle, and medical factors ( 11 ).…”

“…In addition to male sex, older age, obesity, and diabetes are associated with increased risk of intensive care admission and death from COVID-19 ( 5 , 6 , 7 , 8 , 9 ). As men age, testosterone concentrations decline ( 10 ).…”