Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults

IMPORTANCE: Psychiatric disorders may be associated with an increased risk for SARS-CoV-2 breakthrough infection after vaccination, but no studies have tested this hypothesis. OBJECTIVE: To evaluate whether past diagnoses of psychiatric disorders are associated with an increased incidence of SARS-CoV-2 breakthrough infection among fully vaccinated individuals. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included data from the administrative and electronic health records of US Department of Veterans Affairs (VA) patients from February 20, 2020, to November 16, 2021. Participants included 263 697 patients who accessed VA health care during the study period, had at least 1 SARS-CoV-2 test recorded in the electronic health record, had no record of SARS-CoV-2 infection prior to vaccination, and had completed a full SARS-CoV-2 vaccination regimen 14 days or more prior. EXPOSURES: Psychiatric disorder diagnoses in the past 5 years, including depressive, posttraumatic stress, anxiety, adjustment, alcohol use, substance use, bipolar, psychotic, attention-deficit/hyperactivity, dissociative, and eating disorders. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 breakthrough infections, defined as positive SARS-CoV-2 tests, among fully vaccinated individuals. RESULTS: Of 263 697 fully vaccinated VA patients (239 539 men [90.8%]; mean [SD] age, 66.2 [13.8] years), 135 481 (51.4%) had at least 1 psychiatric disorder diagnosis, and 39 109 (14.8%) developed a breakthrough infection. A diagnosis of any psychiatric disorder was associated with increased incidence of breakthrough infection, both in models adjusted for potential confounders (adjusted relative risk [aRR], 1.07; 95% CI, 1.05-1.09) and additionally adjusted for medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05). Most specific psychiatric disorder diagnoses were associated with an increased incidence of breakthrough infection, with the highest relative risk observed for adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) and substance use disorders (aRR, 1.16; 95% CI, 1.12-1.21) in fully adjusted models. Stratifying the sample at 65 years of age revealed that associations between psychiatric diagnoses and incident breakthrough infection were present in both age groups but were stronger and robust to adjustment for medical comorbidities and smoking among older patients. CONCLUSIONS AND RELEVANCE: This cohort study suggests that psychiatric disorder diagnoses were associated with an increased incidence of SARS-CoV-2 breakthrough infection among VA patients, with the strongest associations observed for older individuals. Individuals with psychiatric disorders may be at heightened risk for contracting COVID-19 even after vaccination, suggesting the need for targeted prevention efforts.