Does comorbidity burden explain the higher COVID-19 mortality risk among men? A retrospective cross-sectional analysis of a well-defined cohort of patients in Bronx, New York

Objectives Men have a higher mortality rate and more severe COVID-19 infection than women. The mechanism for this is unclear. We hypothesise that innate sex differences, rather than comorbidity burden, drive higher male mortality. Design Retrospective cohort. Setting Montefiore Health System (MHS) in Bronx, New York, USA. Participants A cohort population of 364 992 patients at MHS between 1 January 2018 and 1 January 2020 was defined, from which individuals hospitalised during the pre-COVID period (1 January 2020-15 February 2020) (n=5856) and individuals hospitalised during the COVID-19 surge (1 March 2020-15 April 2020) (n=4793) were examined for outcomes. A subcohort with confirmed COVID-19+ hospitalisation was also examined (n=1742). Primary and secondary outcome measures Hospitalisation and in-hospital mortality. Results Men were older, had more comorbidities, lower body mass index and were more likely to smoke. Unadjusted logistic regression showed a higher odds of death in hospitalised men than women during both the pre-COVID-19 and COVID-19 periods (pre-COVID-19, OR: 1.66 vs COVID-19 OR: 1.98). After adjustment for relevant clinical and demographic factors, the higher risk of male death attenuated towards the null in the pre-COVID-19 period (OR 1.36, 95% CI 1.05 to 1.76) but remained significantly higher in the COVID-19 period (OR 2.02; 95% CI 1.73 to 2.34). In the subcohort of COVID-19+ hospitalised patients, men had 1.37 higher odds of in-hospital death (95% CI 1.09 to 1.72), which was not altered by adjustment for comorbidity (OR remained at 1.38 (95% CI 1.08 to 1.76)) but was attenuated with addition of initial pulse oximetry on presentation (OR 1.26, 95% CI 0.99 to 1.62). Conclusions Higher male mortality risk during the COVID-19 period despite adjustment for comorbidity supports the role of innate physiological susceptibility to COVID-19 death. Attenuation of higher male risk towards the null after adjustment for severity of lung disease in hospitalised COVID-19+ patients further supports the role of higher severity of COVID-19 pneumonia in men.