Your Mental Health May Impact Your Chances of Breakthrough COVID

Summary: Vaccinated people with a history of mental health disorders including bipolar disorder, psychosis, and anxiety, have a 24% increased risk of contracting COVID-19, a new study reports.

Source: UCSF

A new study led by UC San Francisco has shown that people who are vaccinated against SARS-CoV-2, and have a history of certain psychiatric conditions, have a heightened risk of COVID-19 — a finding that may be related to impaired immune response as well as risky behaviors associated with some disorders. 

The researchers from UCSF and the San Francisco VA Health Care System found that patients over 65 with substance abuse, psychotic disorders, bipolar disorder, adjustment disorder and anxiety, faced increased risks of up to 24% for breakthrough COVID. For those under 65, risks were up to 11% higher than for those without a psychiatric history. 

For both age groups, data was adjusted for age, sex, race, ethnicity and vaccine type, as well as for smoking and underlying conditions like obesity, diabetes, sleep apnea, cardiovascular, lung, kidney and liver diseases, HIV and cancer.

In the study, which publishes on April 14, 2022, in JAMA Network Open, researchers tracked data from more than a quarter of a million U.S. Department of Veterans Affairs patients, who had completed their vaccine regimen and had at least one test for SARS-CoV-2. Just over a half (51.4%) of the patients had received at least one psychiatric diagnosis within the last five years and 14.8% developed breakthrough COVID, confirmed by a positive test.

Waning Immunity, Less Protection to New Variants May Explain Higher Rates

“Our research suggests that increased breakthrough infections in people with psychiatric disorders cannot be entirely explained by socio-demographic factors or pre-existing conditions,” said senior author Aoife O’Donovan, PhD, of the UCSF Weill Institute for Neurosciences and the San Francisco VA Health Care System.

“It’s possible that immunity following vaccination wanes more quickly or more strongly for people with psychiatric disorders and/or they could have less protection to newer variants.”

A study earlier this year, led by the same UCSF researchers, found that people with elevated anxiety and probable post-traumatic stress disorder, conditions associated with impulsivity, were more likely to engage in behaviors that put them at higher risk for COVID.

The average age of the 263,697 participants was 66 and 90.8% were male. Overall, those participants with psychiatric disorders had a 3% increased risk for breakthrough COVID infections in 2021, when adjusted for both demographic factors and pre-existing conditions, compared with participants without a psychiatric history.

But the risk was 24% higher for over-65s with substance abuse, 23% higher for those with psychotic disorders, 16% higher for bipolar disorder, 14% for adjustment disorder and 12% for anxiety. 

Surprisingly, given the greater incidence of breakthrough infections among younger people, this study showed significantly smaller effects in the under-65s group.

Moreover, risks were 10% lower in participants with psychotic disorders compared to those without a psychiatric diagnosis –- a decrease that O’Donovan attributes to possible lower socialization among younger people with psychotic disorders compared with older people who “may be less socially isolated because of their greater burden of ill health and contacts with caregivers.” 

However, risks for breakthrough infections associated with substance abuse, adjustment disorder, anxiety and post-traumatic stress disorder were all higher in the younger cohort than their peers without a psychiatric diagnosis – 11%, 9%, 4% and 3%, respectively.

Higher Need for In-Person Care May Mean Increased Risk 

First author Kristen Nishimi, PhD, also of the UCSF Weill Institute for Neurosciences and the San Francisco VA Health Care System, believes the higher incidence of breakthrough infection among older participants may be due to “decreased immunological response to vaccine that has been associated with some psychiatric disorders, which may be more substantial in older adults.”

This shows a woman in a facemask
It’s also possible that older adults with psychiatric disorders “may require more frequent in-person care, which could increase their interactions with the health care system,” she noted. Image is in the public domain

It’s also possible that older adults with psychiatric disorders “may require more frequent in-person care, which could increase their interactions with the health care system,” she noted. 

Breakthrough risks for other non-psychiatric conditions were also calculated and adjusted for factors like obesity and smoking status, as well as other underlying conditions. The researchers found that patients with chronic kidney disease had an increased risk of 23%, compared with 20% for HIV, 19% for cardiovascular disease, 18% for COPD and 13% for sleep apnea. 

This shows that certain psychiatric conditions, particularly in the 65-plus group, face risks that are on a par with other conditions, said O’Donovan. “Mental health is important to consider in conjunction with other risk factors,” she said, “and some patients should be prioritized for boosters and other critical preventive efforts.” 

Co-Authors: Thomas C. Neylan, MD, of San Francisco VA Health Care System and UCSF Weill Institute for Neurosciences; Daniel Bertenthal, MPH, of San Francisco VA Health Care System; Karen H. Seal, MD, of UCSF Weill Institute for Neurosciences, UCSF Department of Medicine and San Francisco VA Health Care System. 

Funding: This work was supported by a UCSF Department of Psychiatry Rapid Award and UCSF Faculty Resource Fund Award to O’Donovan. Nishimi and Bertenthal are supported by awards from the Department of Veterans Affairs.

About this mental health and COVID-19 research news

Author: Suzanne Leigh
Source: UCSF
Contact: Suzanne Leigh – UCSF
Image: The image is in the public domain

Original Research: Open access.
Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults” by Aoife O’Donovan et al. JAMA Network Open


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


Psychiatric disorders may be associated with an increased risk for SARS-CoV-2 breakthrough infection after vaccination, but no studies have tested this hypothesis.


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.


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.


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.

Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.