Evolution with age of the relationship between sex and post-COVID symptoms: a population-based cohort study

BACKGROUND: It is unclear why women more frequently experience post-COVID symptoms than men. Sex and age-dependent immune dysregulation triggered by SARS-CoV-2 infection might be involved in this association. We assessed whether age modified the association between sex and post-COVID symptoms, and whether this effect modification might be attributable to SARS-CoV-2 infection. METHODS: From the French population-based prospective cohort study with random sampling EpiCov (Spring 2020-Autumn 2022), we included two groups of participants aged ≥ 17: those with a first SARS-CoV-2 confirmed infection during the Omicron wave in 2022 (infected participants, N = 10,618), and those with no SARS-CoV-2 infection history (uninfected participants, N = 28,716). In both groups, we assessed effect modification by age on the association between sex and any self-reported persistent symptom in Autumn 2022 using modified Poisson regressions. RESULTS: Respectively, 10.0% (95% CI: 9.2%, 10.8%) infected participants and 3.1% (95% CI: 2.8%, 3.4%) uninfected participants reported persistent symptoms. In both groups, women more frequently reported persistent symptoms than men (adjusted prevalence ratios (aPRs) [95% CI]: 2.06 [1.70, 2.49] and 1.55 [1.25, 1.92], respectively). However, in infected participants, this association was stronger before than after 35 years (aPRs [95% CI]: 3.54 [2.12, 5.91], 1.77 [1.32, 2.37]; 1.65 [1.20, 2.26]; 1.74 [1.15, 2.63] for 17-34, 35-49, 50-64 and ≥ 65-year-olds, respectively, interaction P = 0.041). We found no effect modification by age in uninfected participants. CONCLUSIONS: Women are a target population in post-COVID symptoms management, especially among younger adults. Sex and age-dependent mechanisms attributable to SARS-CoV-2 infection may be involved in post-COVID symptoms.