Abstract
IMPORTANCE: Sepsis is a major global health concern influenced by both biological sex and socially constructed gender roles, which can affect disease susceptibility, progression, treatment and outcomes. Evidence on sex-specific differences in sepsis often lacks age-specific analysis, despite known interactions between sex, age, and immune function. OBJECTIVE: We aimed to investigate age-dependent associations between sex and mortality as well as long-term outcomes among sepsis survivors after hospitalization. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study based on nationwide health claims data from 2009 to 2017 of 23.0 million beneficiaries of a large German health insurance provider. Patients aged 15 years and older with incident hospital-treated sepsis identified by ICD-10-GM codes in 2013 to 2014 were included. EXPOSURES: Female and male sex. MAIN OUTCOMES AND MEASURES: Differences in 12-months mortality, medical, psychological and cognitive diagnoses, as well as dependency on nursing care by sex and age were analyzed using generalized additive models including sex*age interaction effects. We report average marginal effects (AME) for sex and age as estimates of the adjusted marginal increase or decrease of the event rate of outcomes. RESULTS: We included 159,684 sepsis patients in 2013/2014, of which 75,809 (47.5%) were female and 83,875 (52.5%) were male. The average marginal hospital and 12-months mortality over the observed age distribution was AME = - 2.8% (95% CI, - 3.2%, - 2.3%, P < .001) and AME = - 5.4% (95% CI, - 5.9%, - 4.9%, P < .001) lower in females, respectively. Significant female survival benefits were predominantly found beyond age 44 (hospital mortality) and age 47 (12-months mortality). Females were also less often affected by cognitive impairments, but more often experienced psychological and physical impairments as well as nursing care dependency with differential associations observable across the lifespan. CONCLUSION AND RELEVANCE: Sepsis long-term outcomes appear to be influenced by a complex interaction between age and sex. While our study focuses on these factors, it is important to acknowledge that observed associations cannot be attributed to biological sex alone, as numerous additional factors - directly or indirectly related to sex- may also contribute. These findings underscore the importance of incorporating sex-specific considerations into sepsis care and post-acute support strategies to improve long-term outcomes.