Depressive symptoms and sex differences in the risk of post-COVID-19 persistent symptoms: a prospective population-based cohort study

Women are unexplainedly more affected than men by post-COVID-19 persistent symptoms. Depressive symptoms may partially explain these sex differences. In the French population-based CONSTANCES cohort, depressive symptoms were measured with the nine-item Patient Health Questionnaire between April 6 and May 4, 2020. Between December 2020 and January 2021, among 2,093 infected participants (mean (s.d.) age, 43.0 years (11.9); 55.3% women), 453 (21.6%) reported ≥1 new persistent symptom that emerged from March 2020. Accounting for several confounders, women were more likely than men to have ≥1 symptom (odds ratio (95% confidence interval), 1.45 (1.17–1.80)). Further adjusting for the nine-item Patient Health Questionnaire, participants in the highest (versus lowest) quartile were more likely to have ≥1 symptom (2.97 (2.09–4.23)), while the association with female sex substantially dropped (1.28 (1.02–1.60)). Depressive symptoms mediated 41.5–45.4% of this association. A biopsychosocial model, integrating gender and mental health, is warranted to understand long COVID and inform preventive and therapeutic strategies.