Mental Illness Tied to COVID-19 Breakthrough Infection

Megan Brooks

April 20, 2022

Psychiatric disorders are tied to an increased risk of COVID-19 breakthrough infection, particularly among older adults, new research shows.

"Psychiatric disorders remained significantly associated with incident breakthrough infections above and beyond sociodemographic and medical factors, suggesting that mental health is important to consider in conjunction with other risk factors," the investigators, led by Aoife O’Donovan, PhD, University of California, San Francisco, write.

Individuals with psychiatric disorders "should be prioritized for booster vaccinations and other critical preventive efforts, including increased SARS-CoV-2 screening, public health campaigns, or COVID-19 discussions during clinical care," they add.

The study was published online April 14 in JAMA Network Open

Elderly Most Vulnerable

The researchers reviewed the records of 263,697 veterans who were fully vaccinated against COVID-19.

Just over a half (51.4%) had one or more psychiatric diagnoses within the last 5 years and 14.8% developed breakthrough COVID-19 infections, confirmed by a positive SARS-CoV-2 test.

Psychiatric diagnoses among the veterans included depression, post-traumatic stress, anxiety, adjustment disorder, substance use disorder, bipolar disorder, psychosis, attention deficit hyperactivity disorder (ADHD), dissociation, and eating disorders.

In the overall sample, a history of any psychiatric disorder was associated with a 7% higher incidence of breakthrough COVID-19 infection in models adjusted for potential confounders (adjusted relative risk [aRR], 1.07; 95% CI, 1.05-1.09) and a 3% higher incidence in models additionally adjusted for underlying medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05).

Most psychiatric disorders were associated with a higher incidence of breakthrough infection, with the highest relative risk observed for substance use disorders (aRR, 1.16; 95% CI, 1.12 -1.21) and adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) in fully adjusted models.

Older vaccinated veterans with psychiatric illnesses appear to be most vulnerable to COVID-19 reinfection.

In veterans aged 65 and older, all psychiatric disorders were associated with an increased incidence of breakthrough infection, with increases in the incidence rate ranging from 3% to 24% in fully adjusted models.

In the younger veterans, in contrast, only anxiety, adjustment, and substance use disorders were associated with an increased incidence of breakthrough infection in fully adjusted models.

Psychotic disorders were associated with a 10% lower incidence of breakthrough infection among younger veterans, perhaps due to greater social isolation, the researchers say.

Risky Behavior or Impaired Immunity?

"Although some of the larger observed effect sizes are compelling at an individual level, even the relatively modest effect sizes may have a large effect at the population level when considering the high prevalence of psychiatric disorders and the global reach and scale of the pandemic," O’Donovan and colleagues write.

They note that psychiatric disorders, including depression, schizophrenia, and bipolar disorders, have been associated with impaired cellular immunity and blunted response to vaccines. Therefore, it’s possible that those with psychiatric disorders have poorer responses to COVID-19 vaccination.

It’s also possible that immunity following vaccination wanes more quickly or more strongly in people with psychiatric disorders and they could have less protection against new variants, they add.

Patients with psychiatric disorders could be more apt to engage in risky behaviors for contracting COVID-19, which could also increase the risk for breakthrough infection, they say.

The study was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award. O’Donovan reports no relevant disclosures. 

JAMA Network Open. Published online April 14, 2022. Full text.

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