Increased incidence of COVID-19 breakthrough cases associated with psychiatric disorders

Increased incidence of COVID-19 breakthrough cases associated with psychiatric disorders

In a recent study published in JAMA Network Open, researchers investigated the relationship between past psychiatric disorder diagnoses and breakthrough cases of coronavirus disease 2019 (COVID-19) in fully vaccinated people.

Study: Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults. Image Credit: GEMINI PRO STUDIO/Shutterstock


In the United States (US), more than 68% of the general population aged 12 years or above were fully vaccinated by November 2021. In comparison, around 63.8% of US Department of Veterans Affairs (VA) patients were fully vaccinated by October 2021. However, many vaccine-breakthrough cases have been documented given the incomplete vaccination coverage, waning immunity, and emergent immune-resistant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants.

Before COVID-19 vaccines were introduced, people with psychiatric disorders were at an elevated risk of severe disease outcomes. Therefore, it is necessary to examine if the same holds for breakthrough cases among this vulnerable population to implement targeted prophylactic measures such as booster vaccination.

About the study

In the current study, researchers evaluated whether psychiatric disorders were associated with the incidence of COVID-19 vaccine breakthrough cases among fully vaccinated subjects.

People who sought VA healthcare across the US from February 20, 2020, to November 16, 2021, were included in the study. These subjects took at least one COVID-19 test during the study period and were fully vaccinated with no history of COVID-19 before vaccination. Fully vaccinated were those who received two doses of messenger ribonucleic acid (mRNA) vaccines (Pfizer’s BNT162b2 or Moderna’s mRNA-1273) or one dose of Janssen’s COVID-19 vaccine.

Psychiatric disorder diagnoses were identified from in- or outpatient clinical data from the past five years. They included post-traumatic stress disorder (PTSD), depressive disorder, adjustment disorder, anxiety disorder, substance or alcohol use disorders, bipolar disorders, dissociative disorders, eating disorders, and attention-deficit or hyperactivity disorder.

A breakthrough infection was defined as a positive COVID-19 case recorded in the VA clinical notes. The association between psychiatric disorder diagnoses and COVID-19 breakthrough incidence was estimated by computing relative risks (RRs) using the Poisson regression approach with robust error variance. Potential confounders like sociodemographic parameters, type of vaccine, and time since vaccine administration were adjusted in one model. A second model (model 2) additionally adjusted for medical comorbidities, smoking, and obesity.


Among the 263,697 fully vaccinated patients who sought VA healthcare services, nearly 91% were males, and more than 51% had a psychiatric disorder in the past five years. About 70% of them were White, 20.5% Black, 8.3% were Hispanic, and 9.3% were of unknown race. Breakthrough cases were recorded in 39,109 patients (14.8%).

A 7% higher incidence of vaccine breakthrough infection was observed in those with the prior psychiatric disorder than in those without psychiatric disorders when adjusted for potential confounders (model 1). A further 3.7% attenuation was observed in the estimates and was statistically significant when adjusted for medical conditions, smoking, and obesity (model 2). Adjustment disorder and substance use disorders were associated with the highest incidence of breakthrough cases.

Psychotic disorders were not associated with increased breakthrough infection incidence after additional adjustment (model 2). Nearly 16% of people below 65 years had a breakthrough infection compared to 14.2% of breakthrough cases in those aged 65 years or older, indicating that younger age was associated with increased incident breakthrough infections.

When adjusted for potential confounders, a higher incidence of breakthrough infections was associated with any psychiatric disorder for younger and older patients. Divergent results were observed when adjusted for additional confounders (model 2). For instance, except for psychotic and bipolar disorders among younger patients, individual psychiatric disorders were associated with a higher incidence of breakthrough cases. Still, no such associations were evident for PTSD, depressive, and alcohol use disorders when adjusted for smoking, obesity, and medical conditions.

Conversely, other than alcohol use disorder and PTSD, psychiatric disorders were associated with increased breakthrough case incidence among older patients. A lower incidence of SARS-CoV-2 breakthrough infections was associated with psychotic disorders among younger patients, but a higher incidence was observed in older patients.


Based on the findings, the researchers noted that fully vaccinated VA patients with prior psychiatric disorder diagnoses had elevated SARS-CoV-2 breakthrough infections compared to those without any psychiatric disorders. In fully adjusted models, results were variable among younger and older subjects. In older patients, all specific psychiatric disorders were associated with a 3% – 24% increase in the incidence of breakthrough cases when adjusted for potential and additional confounders.

About 10% lower incidence of breakthrough infections was associated with psychotic disorders among younger patients relative to older patients. These findings indicated that besides socioeconomic factors, vaccine types and timing, obesity, smoking, or medical conditions, psychiatric diagnoses might be an independent risk factor for increased COVID-19 breakthrough cases. Therefore, the authors suggested that this vulnerable population be prioritized for a booster vaccination and other prophylactic measures.

Journal reference:
  • Nishimi K, Neylan TC, Bertenthal D, Seal KH, O’Donovan A. (2022). Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults. JAMA Network Opendoi: 10.1001/jamanetworkopen.2022.7287

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Adjustment Disorder, Alcohol, Anxiety, Anxiety Disorder, Coronavirus, Coronavirus Disease COVID-19, covid-19, Depressive Disorder, Healthcare, Hyperactivity, immunity, Obesity, Post-Traumatic Stress Disorder, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Smoking, Stress, Syndrome, Vaccine, Veterans Affairs

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Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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