COVID-19 breakthrough infections were more common among patients with psychiatric disorder diagnoses, according to results of a retrospective cohort study, published in JAMA Network Open.

Investigators at the San Francisco Veterans Affairs (VA) Health Care System evaluated VA health records between February 2020 and November 2021. Individuals (N=263,697) who accessed care during the study period and were tested for SARS-CoV-2 were evaluated for positivity, vaccination status, and psychiatric disorder diagnoses in the previous 5 years. A breakthrough infection was defined as a positive SARS-CoV-2 test >14 days after full vaccination status.

The study population was 90.8% men, aged mean 66.2 (SD, 13.8) years, 70.1% were White, 36.4% had diabetes, 35.7% had cardiovascular disease, and 31.0% had obstructive sleep apnea. Most of the population (51.4%) had any psychiatric disorder. Stratified by the presence of any psychiatric disorder, all characteristics differed from those without a psychiatric condition (all P <.001).

Continue Reading

A total of 39,109 (14.8%) breakthrough infections were observed.

Among the entire study cohort, breakthrough infections were associated with age, ethnicity, time since vaccination, vaccine type, the interaction between type of vaccine and time since vaccination, and all comorbidities.

Breakthrough infections were more likely to occur among the cohort with psychiatric disorders (adjusted relative risk [aRR], 1.07; 95% CI, 1.05-1.09; P <.001). These findings were partially attenuated after correcting for medical conditions, obesity, and smoking status (aRR, 1.03; 95% CI, 1.01-1.05; P <.001).

Stratified by psychiatric disorder, those with substance use disorder (aRR, 1.16), adjustment disorder (aRR, 1.13), anxiety disorder (aRR, 1.08), bipolar disorder (aRR, 1.07), major depressive disorder (aRR, 1.05), alcohol use disorder (aRR, 1.05), and posttraumatic stress disorder (aRR, 1.03) were at an increased risk for breakthrough infection (all P ≤.006). Patients with psychotic disorder tended to be at increased risk, but the risk was attenuated in the fully adjusted model (aRR, 1.05; 95% CI, 0.99-1.11; P =.09).

Stratified by age, younger individuals (age <65 years) with substance use disorder (aRR, 1.11; P <.001), adjustment disorder (aRR, 1.09; P <.001), and anxiety disorder (aRR, 1.04; P =.01) were at increased risk for breakthrough infection and those with psychotic disorder (aRR, 0.90; P =.009) at decreased risk. In the older cohort, substance use disorder (aRR, 1.24), psychotic disorder (aRR, 1.23), bipolar disorder (aRR, 1.16), adjustment disorder (aRR, 1.14), anxiety disorder (aRR, 1.12), and major depressive disorder (aRR, 1.08) were associated with an increased risk for breakthrough infection (all P <.001).

This study could not account for breakthrough infections that were detected outside the VA system.

The study authors concluded, “In this large-scale cohort study of VA patients, psychiatric disorders were associated with an increased incidence of SARS-CoV-2 breakthrough infections, with robust associations among older veterans. In fully adjusted models, individual psychiatric disorders were associated with a 3% to 16% increased incidence of breakthrough infection in our sample, which is comparable to the 7% to 23% increased incidence of breakthrough infection that we observed for physical comorbidities (eg, cancer, kidney disease, and cardiovascular disease).”

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Nishimi K, Neylan TC, Bertenthal D, Seal KH, O’Donovan A. Association of psychiatric disorders with incidence of SARS-CoV-2 breakthrough infection among vaccinated adults. JAMA Netw Open. 2022;5(4):e227287. doi:10.1001/jamanetworkopen.2022.7287