Comparison of Depression and Anxiety Following Self-reported COVID-19-Like Symptoms vs SARS-CoV-2 Seropositivity in France.

Importance: The long-term consequences of COVID-19 on mental health are a critical issue given the number of people infected with SARS-CoV-2 worldwide since the beginning of the pandemic. Objective: To investigate the associations between self-reported COVID-19-like symptoms or SARS-CoV-2 seropositivity and subsequent depression or anxiety. Design, Setting, and Participants: This propensity score-matched cohort study began in May 2020, with follow-ups in November 2020 and July 2021. The study used data from a large, randomly selected, national population-based cohort from France, the EpiCoV (Epidémiologie et Conditions de Vie) study. Of 85 074 individuals 15 years or older who completed the questionnaires at the 3 collection times, 28 568 were excluded because they did not return a blood sample for serologic testing, 1994 because of missing data on outcomes or exposures, and 9252 to respect the temporal sequence (exposure must precede the outcome). Exposures: Propensity scores based on various socioeconomic, lifestyle, and health variables were computed to match participants who experienced COVID-19-like symptoms between February and November 2020 or showed SARS-CoV-2 seropositivity in November 2020. Main Outcomes and Measures: Logistic regression models were used to estimate associations between these occurrences and depression or anxiety assessed in July 2021 using the Patient Health Questionnaire 9-item and Generalized Anxiety Disorder 7-item scales, respectively. Results: Among the 45 260 included participants (mean [SD] age, 51.1 [18.9] years; 52.4% women; 8.0% with depression and 5.3% with anxiety in July 2021), COVID-19-like symptoms were associated with subsequent depression (adjusted odds ratio, 1.70; 95% CI, 1.45-1.99) and anxiety (adjusted OR, 1.57; 95% CI, 1.29-1.92), whereas SARS-CoV-2 seropositivity was not. Furthermore, COVID-19-like symptoms, but not anosmia or dysgeusia alone, were associated with subsequent depression and anxiety in both the seropositive and seronegative subgroups. Conclusions and Relevance: In this cohort study of more than 45 000 individuals drawn from the French general population, SARS-CoV-2 infection was not found as a risk factor of subsequent depression or anxiety. Moreover, self-reported COVID-19-like symptoms were associated with depression and anxiety assessed at least 8 months later in both seropositive and seronegative subgroups, suggesting that factors other than SARS-CoV-2 infection are implied in this association.