Study Shows Heightened Risk of Breakthrough COVID-19 in Patients with Psychosis, Substance Abuse, Anxiety


Findings demonstrate that patients with certain psychiatric conditions, particularly those aged 65 and older, face risks that are on par with other conditions.

Researchers from the University of California San Francisco have found that individuals who are vaccinated against SARS-CoV-2 and have a history of certain psychiatric conditions may have a heightened risk of breakthrough COVID-19 infection.

The investigators found that patients over the age of 65 with substance abuse, psychotic disorders, bipolar disorder, adjustment disorder, and anxiety faced increased risks up to 24% for breakthrough COVID-19. For those under 65 years of age, risks were up to 11% higher than for those without a psychiatric history.

Data for both age groups were adjusted for age, sex, race, ethnicity, and vaccine type, as well as for smoking and underlying conditions, such as obesity, diabetes, sleep apnea, cardiovascular, lung, kidney and liver diseases, HIV, and cancer. The findings could be related to impaired immune responses in patients with certain psychiatric conditions, as well as risky behaviors associated with some disorders.

In the study, investigators tracked data from more than one-quarter of a million United States Department of Veterans Affairs patients, who had completed their COVID-19 vaccine regimen and had at least 1 test for SARS-CoV-2. Just over half (51.4%) of the patients had received at least 1 psychiatric diagnosis within the past 5 years, and 14.8% developed breakthrough COVID-19 confirmed by a positive test. The average age of the 263,697 participants was 66 years and 90.8% were male.

“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, in a press release. “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.”

An earlier study led by the same researchers found that individuals 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 of COVID-19.

According to the new study, participants with psychiatric disorders had an overall 3% increased risk for breakthrough COVID-19 infections in 2021 compared with participants without a psychiatric history. However, the risk was 24% higher for individuals over 65 years of age with substance abuse, 23% higher for those with psychotic disorders, 16% higher for those with bipolar disorder, 14% higher for patients with adjustment disorder, and 12% for individuals with anxiety.

Surprisingly, given the greater incidence of breakthrough infections among younger individuals, the study showed significantly smaller effects in those under 65 years of age. Moreover, risks were 10% lower in participants with psychotic disorders compared to those without a psychiatric diagnosis, which O’Donovan attributed to possible lower socialization among younger patients with psychiatric disorders. She noted that older patients “may be less socially isolated because of their greater burden of ill health and contacts with caregivers.”

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

A potential reason for the higher incidence of breakthrough infections among older participants could be due to a lower immunological response to the vaccines, which has been associated with some psychiatric disorders and could be more substantial among older adults, according to the study. It is also possible that older adults with psychiatric disorders may require more frequent in-person care, thereby increasing their risk of contracting COVID-19 from a health care provider.

To provide context, breakthrough risk for other non-psychiatric conditions were also calculated and adjusted for factors such as 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. These findings demonstrate that patients with certain psychiatric conditions, particularly those 65 years of age and older, face risks that are on par with other conditions, according to the study authors.

“Mental health is important to consider in conjunction with other risk factors, and some patients should be prioritized for boosters and other critical preventive efforts,” O’Donovan concluded in the press release.


Your Mental Health May Impact Your Chances of Breakthrough COVID. News release. University of California San Francisco; April 14, 2022. Accessed April 20, 2022.

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