Sex differences in the outcome of critically Ill patients with COVID-19 - An international multicenter critical care consortium study

Abstract

Background

Sex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown.

Objectives

To determine the effects of sex on ICU mortality in patients with COVID-19

Methods

This retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay.

Results

Overall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49–68) and 59 (IQR=49–67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02–1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05–1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01–1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16–1.62) and PE (aOR=1.28; 95 % CI=1.06–1.55).

Conclusion

Among patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest.