Sex-specific patterns of symptom burden, psychological distress, and work productivity impairment in post-acute sequelae of COVID-19: a 10-month dynamic cohort study.

backgroundA considerable proportion of patients experience post-acute sequelae of COVID-19 (PASC). Increasing evidence suggests sex-related differences, yet systematic longitudinal analyses remain limited. This study aimed to examine sex-specific differences in symptoms, psychological burden, work productivity and physical activity over ten months following acute COVID-19.

methodsIn this prospective, dynamically enrolled cohort study, patients with ongoing symptoms after confirmed SARS-CoV-2 infection were followed over a 10-month observation period. Patients conducted at the post-COVID outpatient clinic of the department of respiratory medicine and infectious diseases at Hannover Medical School, Germany. The assessment included patient-reported outcome measures, pulmonary function tests, six-minute walk tests, and capillary blood gas analysis. All outcome comparisons between sexes were adjusted for age, BMI, COVID-19 severity, and comorbidities using generalised linear mixed-effects models, with sex-by-time interaction terms tested to assess whether differences changed over follow-up, and p-values corrected for multiple testing across all outcome comparisons using the Holm method. A sensitivity analysis was performed in the subgroup of patients with complete follow-up at all four visits.

resultsFive hundred ninety patients attended to our clinic and a total of 433 patients were eligible and consecutively enrolled. Males were older (56 years vs. 52 years, p = 0.002), had more cardiovascular comorbidities (16% vs. 5%, p < 0.001), and experienced more severe COVID-19 (28% vs. 8%, p < 0.001). After adjustment for age, BMI, COVID-19 severity, and comorbidities, and Holm correction for multiple testing across all 27 outcome comparisons, females showed higher fatigue (Fatigue Assessment Scale, adjusted β = 3.3, Holm-adjusted p = 0.006), higher anxiety (GAD-2, β = 0.5, p = 0.021), lower quality of life (EQ-5D-3L, β = -0.6, p = 0.004), and greater work productivity impairment, both as a continuous score (WPAI-VAS, β = 1.3, p = 0.031) and as a binary indicator of clinically relevant impairment (OR = 3.0, p = 0.020). Females also had higher percent-predicted (pp) total lung capacity (p < 0.0001) and lower pCO

conclusionsAfter accounting for baseline imbalance in age, BMI, COVID-19 severity, and comorbidities, and after correcting for multiple testing, sex-specific differences persisted for fatigue, anxiety, quality of life, and work productivity impairment, as well as selected lung function parameters. These differences did not change significantly across the 10-month observation period and did not show a significant sex-by-time interaction. The findings support the need for individualised, sex-specific follow-up focused on fatigue, psychological burden, and work productivity in patients with PASC.