Sex-Based Differences in COVID-19 Outcomes

Abstract

Background: Smaller studies suggest lower morbidity and mortality associated with coronavirus disease 2019 (COVID-19) in women. Our aim is to assess the impact of female sex on outcomes in a large cohort of patients hospitalized with COVID-19. Materials and Methods: This is a retrospective observational cohort study of 10,630 adult patients hospitalized with a confirmed COVID-19 polymerase chain reaction between March 1, 2020 and April 27, 2020, with follow-up conducted through June 4, 2020. Logistic regression was used to examine the relationship between sex and the primary outcomes, including length of stay, admission to intensive care unit (ICU), need for mechanical ventilation, pressor requirement, and all-cause mortality as well as major adverse events and in-hospital COVID-19 treatments. Results: In the multivariable analysis, women had 27% lower odds of in-hospital mortality (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.66-0.81; p < 0.001), 24% lower odds of ICU admission (OR = 0.76, 95% CI 0.69-0.84; p < 0.001), 26% lower odds of mechanical ventilation (OR = 0.74, 95% CI 0.66-0.82; p < 0.001), and 25% lower odds of vasopressor requirement (OR = 0.75, 95% CI 0.67-0.84; p < 0.001). Women had 34% less odds of having acute cardiac injury (OR = 0.66, 95% CI 0.59-0.74; p < 0.001; n = 7,289), 16% less odds of acute kidney injury (OR = 0.84, 95% CI 0.76-0.92; p < 0.001; n = 9,840), and 27% less odds of venous thromboembolism (OR = 0.73, 95% CI 0.56-0.96; p < 0.02; c-statistic 0.85, n = 9,407). Conclusions: Female sex is associated with lower odds of in-hospital outcomes, major adverse events, and all-cause mortality. There may be protective mechanisms inherent to female sex, which explain differences in COVID-19 outcomes.

Keywords: COVID-19; gender; hospital outcomes; intensive care; mortality; sex.

FIG. 1.

Analysis consort flow diagram. Inclusion and exclusion criteria applied to 11,265 COVID-19 inpatients at a single health system admitted from March 1, 2020 and April 27, 2020 with follow-up conducted through June 4, 2020.

FIG. 2.

VTE consort flow diagram. Inclusion and exclusion criteria applied to data obtained from a separate VTE outcomes radiology database in a single health system, including 11,265 COVID-19 inpatients admitted between March 1, 2020 and April 28, 2020 with follow-up conducted through April 30, 2020. CCI, Charlson Comorbidity Index; VTE, venous thromboembolism.

FIG. 3.

Forest plot of primary outcomes and major adverse events. Forest Plot showing the odds ratio for primary outcomes, after controlling for age, ethnicity/race, insurance [included in final models for in-hospital mortality and LOS only], BMI, CCI, LNR, D-dimer, CRP, ferritin and antiplatelet/anticoagulation in 10,630 COVID-19 inpatients meeting eligibility criteria at a single health system admitted from March 1, 2020 and April 27, 2020 with follow-up conducted through June 4, 2020. ACI, acute cardiac injury; AKI, acute kidney injury; ASLI, acute severe liver injury; BMI, body mass index; CRP, C-reactive protein; ICU, intensive care unit; LNR, lymphocyte-to-neutrophil ratio; LOS, length of stay.