Association of COVID-19 with mental illnesses in vaccinated and unvaccinated people: a population-based cohort study in OpenSAFELY

Importance: COVID-19 is associated with subsequent mental illness in both hospital- and population-based studies. However, evidence regarding which mental illnesses are associated with COVID-19 by vaccination status in these populations is limited. Objective: Determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalised patients and the general population Design: We defined three cohorts: a ‘pre-vaccine availability’ cohort followed during the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts followed during the Delta variant era (June-December 2021). Setting: With NHS England approval, we used OpenSAFELY-TPP to access linked data from 24 million people registered with English general practices (GPs) using TPP SystmOne. Participants: People registered with an English GP for at least six months and alive with a known age between 18 and 110 years, sex, deprivation, and region at baseline. People were excluded if they had COVID-19 before baseline. Cohort specific criteria also applied. Exposure: Confirmed COVID-19 diagnosis recorded in primary care; secondary care; testing data or the death registry. Main outcomes and measures: Adjusted hazard ratios (aHRs) comparing the incidence of mental illnesses after diagnosis of COVID-19 with the incidence before or without COVID-19 for depression, serious mental illness, general anxiety, post-traumatic stress disorder, eating disorders, addiction, self-harm, and suicide. Results: The largest cohort, pre-vaccine availability, included 18,648,606 people with a median age of 49 years. This cohort was 50.2% female. Incidence of most outcomes was elevated during weeks 1-4 after COVID-19 diagnosis, compared with before or without COVID-19, in each cohort. Vaccination mitigated the adverse effects of COVID-19 on mental health: aHRs (95% CIs) for depression and for serious mental illness during weeks 1-4 after COVID-19 were 1.93 (1.88-1.98) and 1.49 (1.41-1.57) in the pre-vaccine availability cohort and 1.79 (1.68-1.90) and 1.45 (1.27-1.65) in the unvaccinated cohort, compared with 1.16 (1.12-1.20) and 0.91 (0.85-0.98) in the vaccinated cohort. Elevation in incidence was higher, and persisted for longer, after hospitalised COVID-19. Conclusions and Relevance: Incidence of mental illnesses is elevated for up to a year following severe COVID-19 in unvaccinated people. Vaccination mitigates the adverse effect of COVID-19 on mental health.</p