Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population

Abstract

Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n = 26,101), contemporary control with no evidence of infection (n = 380,337) and historical control predating the pandemic (n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42-1.67; P = 1.70 × 10^-24; difference in incidence rate: 27.36, 95% CI 21.16-34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70-2.78; P = 5.80 × 10^-10) than those not hospitalized (1.41, 1.30-1.53; P = 1.46 × 10^-16), and were reduced in fully vaccinated people (0.97, 0.80-1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49-1.79; P = 4.95 × 10^-26). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78-1.07; P = 0.278) but increased prescription risk (1.42, 1.00-2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.

Fig. 1

Flowchart of study design and cohort construction.

Fig. 2. Risks of incident psychiatric diagnoses and psychotropic prescriptions after SARS-CoV-2 infection compared with the contemporary control group.

Mental health outcomes were ascertained after SARS-CoV-2 infection until the end of follow-up. Results compare the SARS-CoV-2 infection group (n = 19,353) to the contemporary control group with no evidence of infection (n = 301,398). HRs were adjusted for predefined and data-driven covariates. Risk was reported in relative scale (HRs and 95% CIs) and absolute scale (absolute risk difference (ARD) per 1,000 person-years with 95 CIs). Squares represent estimates of HRs (with area inversely proportional to the variance) or risk difference, and error bars represent the corresponding 95% CIs. GAD, generalized anxiety disorder; PTSD, post-traumatic stress disorder.

Fig. 3. Risks of composite mental health outcomes after SARS-CoV-2 infection compared with the contemporary control group.

Mental health outcomes were ascertained after SARS-CoV-2 infection until the end of follow-up. Results compare the SARS-CoV-2 infection group (n = 19,353) to the contemporary control group with no evidence of infection (n = 301,398). HRs were adjusted for predefined and data-driven covariates. Risk was reported in relative scale (HRs and 95% CIs) and absolute scale (absolute risk difference per 1,000 person-years with 95 CIs). Squares represent estimates of HRs (with area inversely proportional to the variance) or risk difference, and error bars represent the corresponding 95% CIs.

Fig. 4. Cumulative incidence curves of mental health outcomes after SARS-CoV-2 infection compared with the contemporary control group.

Mental health outcomes were ascertained after SARS-CoV-2 infection until the end of follow-up. Results compare the SARS-CoV-2 infection group (n = 19,353) to the contemporary control group with no evidence of infection (n = 301,398). HRs were adjusted for predefined and data-driven covariates. The shading around plotted lines shows 95% CIs. a–c, incident outcome; d–f, incident or recurrent outcome.

Fig. 5. Subgroup analyses of the risks of incident mental health outcomes after SARS-CoV-2 infection compared with the contemporary control group.

Mental health outcomes were ascertained after SARS-CoV-2 infection until the end of follow-up. Results compare the SARS-CoV-2 infection group (n = 19,353) to the contemporary control group with no evidence of infection (n = 301,398) by predefined subgroups. HRs were adjusted for predefined and data-driven covariates where applicable. The calendar period was stratified according to the timeline of UK government coronavirus lockdowns and measures when England entered its third national lockdown on 6 January 2021.

Fig. 6. Risks of psychiatric diagnoses and psychotropic prescriptions by vaccination status and test setting of participants in the SARS-CoV-2 infection group compared with the contemporary control group.

Mental health outcomes were ascertained after SARS-CoV-2 infection until the end of follow-up. HRs were adjusted for predefined and data-driven covariates. a, Analyses by vaccination status. To account for health behaviours related to vaccines, the breakthrough infection (BTI) group (n = 6,453) was compared to the vaccinated control group (n = 117,540), and the non-BTI group (n = 12,900) to the unvaccinated or partially vaccinated control group (n = 183,858). b, Analyses by test setting. Results compare the SARS-CoV-2 infection group by test setting (hospital setting n = 2,541; community setting n = 16,812) to the contemporary control group with no evidence of infection (n = 301,398).