Gender differences and psychosocial stress in upper respiratory tract infections: insights from healthy and hematological cancer cohorts

Abstract Background Upper respiratory tract infections (URTIs) are shaped by sex and gender, with stress potentially playing a critical role. However, the interplay remains poorly understood. This study examined whether women experience higher stress than men, contributing to increased URTI susceptibility and symptom burden. Methods Our monocentric, prospective study included 273 healthy individuals (cohort H) and 194 stem-cell recipients (cohort P), enrolled between 11/2013 and 05/2017. Participants were aged ≥ 18 years. Data included demographics, household composition, smoking behavior, cancer-related characteristics, URTI-symptoms, and perceived stress (measured via 4-item perceived stress scale, PSS-4). Participants were categorized by biological sex, assuming alignment with gender. Results In cohort H (50% women, mostly ≤ 30 years), women reported more moderate/severe URTI-symptoms than men (57% vs. 36%, p < 0.001, φ = 0.210) and higher PSS-4 scores t(271) = 2.84, p < 0.001, d = 0.636. In women, stress modestly correlated with symptom burden ( r = 0.15, p = 0.04). Sex and age were significant predictors of stress. In cohort P (40.5% women, mostly ≥ 30 years), men reported more URTI symptoms (83% vs. 68%, p = 0.021), while PSS-4 did not differ by sex. Stress correlated with symptom burden ( r = 0.293, p < 0.001), particularly in women ( r = 0.385, p < 0.001). Symptom burden was the only independent predictor of stress. Conclusion The relationship between sex, stress, and URTI burden varies by health status. Healthy women, especially younger adults, experience higher stress and more severe symptoms, though stress only modestly relates to symptom burden. In immunocompromised patients, stress strongly reflects symptom severity, particularly in women, with minimal sex differences in stress. These findings highlight a complex interplay between sex, psychosocial stress, and infection outcomes, emphasizing the need for interventions addressing both biological and psychosocial determinants, particularly in vulnerable populations. Trial registration Registry: the German Clinical Trials Register Clinical Trial Number: DRKS00005367 Registration date: 10/17/2013