COVID-19 Greatly Increases Mortality Risk for Schizophrenia Patients, Research Shows

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Individuals with schizophrenia spectrum disorders appear to have more than twice the risk of dying from illnesses related to COVID-19 than do those without schizophrenia, according to two separate reports by researchers in the United States and Israel.

The U.S. study was published in JAMA Psychiatry; the Israeli study was published in Schizophrenia Bulletin.

The striking findings are underscored by the fact that in both studies, the risk remained significantly higher for COVID-related mortality even after controlling for comorbid medical conditions.

“We believe that our results argue for prioritization for vaccination of people with schizophrenia since our results indicate that a diagnosis of schizophrenia is second only to old age as a risk factor [for worse outcomes from COVID-19],” said Donald Goff, M.D., director of the Nathan Kline Institute, vice chair for research at NYU Grossman School of Medicine, and a senior author of the JAMA paper. “Health care systems, clinicians, and family members should also encourage precautionary measures such as mask wearing and social distancing, particularly for people with schizophrenia in congregate living situations.”

The lead author of the JAMA paper was Katlyn Nemani, M.D., of NYU Langone Health. In the study, Goff, Nemani, and colleagues analyzed data from the electronic health records of 7,348 adults, aged 18 years or older, who tested positive for COVID-19 (SARS-CoV-2) between March 3 and May 31, 2020, in the NYU Langone Health System. The system includes more than 260 outpatient office sites and four acute care hospitals in Brooklyn, Long Island, and Manhattan, N.Y.

The authors classified these patients into one of three groups: those with schizophrenia spectrum disorders (n=75), mood disorders (n=564), and anxiety disorders (n=360). Patients in each category were compared with 6,349 patients who did not have psychiatric diagnoses documented before March 3, 2020.

Overall, 864 patients (11.8%) died or were discharged to hospice within 45 days of a positive test result. The researchers found that after adjusting for demographic factors (age, sex, and race), patients with schizophrenia spectrum disorders were 2.87 times more likely to die from COVID-19 within 45 days of testing positive than individuals with no mental illness. After adjusting for medical risk factors, patients with schizophrenia spectrum disorders remained 2.67 times more likely to die from COVID-19 within 45 days of testing positive for the virus than individuals with no mental illness.

The researchers did not find any increased risk of death from COVID-19 among patients with mood and anxiety disorders.

Noting that previous research has shown patients with serious mental illness are 2.5 times more likely to die from any cause than the general population, Goff said they had undertaken the study with the hypothesis that patients with schizophrenia would likely have the highest risk for hospitalization and death related to COVID-19.

“We expected, however, that after we adjusted for preexisting risk factors such as cigarette smoking, heart disease, pulmonary disease, and kidney disease, the magnitude of the effect of schizophrenia on COVID mortality would be less than a 2.5-fold risk, whereas it was actually larger,” Goff said. “Others have found higher infection rates and increased mortality rates among people with serious mental illness, but this was the first study to compare diagnostic categories and to control for other risk factors.”

Goff said there are several possible explanations for why people with schizophrenia may be at higher risk from COVID-19 that will require further research. There is evidence to suggest that schizophrenia may put people at greater risk of immune dysfunction, he noted.

“The other possible factor is that medications may play a role—we are also examining this possibility,” Goff said. “Since we studied only people who had been diagnosed with COVID infection and were already receiving treatment within the NYU Langone Health System, it is less likely that the increased mortality was the result of less access to medical care, though it is a vulnerability for many people with schizophrenia.”

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In the Schizophrenia Bulletin study, lead author Dana Tzur-Bitan, Ph.D., and colleagues found strikingly similar results. She is an assistant professor in the Department of Behavioral Sciences at Ariel University and a clinical psychologist at Shalvata Mental Health Center in Israel.

She and colleagues assessed the odds of significant COVID-19 morbidity and mortality among 25,539 schizophrenia patients receiving care from Clalit Health Services, Israel’s largest health care organization, compared with age- and gender-matched controls. Those with schizophrenia were 2.15 times as likely to be hospitalized for COVID-19 and 3.27 times more likely to die from COVID-19. The association remained significant after controlling for demographic and medical risk factors.

In an interview with Psychiatric News, Tzur-Bitan cited another finding in the JAMA study that mirrored her own research: Just 1.1% of the JAMA study cohort with schizophrenia was positive for infection with COVID (compared with 7.7% of the cohort with mood disorders), yet their risk for hospitalization and death was dramatically higher.

“Though a smaller number are being infected, they have a more serious outcome, tend to be hospitalized more, and are more likely to die,” she said.

Tzur-Bitan said follow-up research will look at whether patients with schizophrenia are receiving vaccinations. Israel has been vigorously proactive in reaching out to citizens, she noted, with 35% of the population—including 79% of individuals over the age of 60—having received at least a first vaccine as of early February.

Like Goff, she says her research argues strongly for prioritizing the vaccination of patients with schizophrenia along with the elderly.

But Tzur-Bitan wonders if patients will follow through. She noted that much previous research has shown that patients with schizophrenia are slower or less likely to receive care for all manner of medical illnesses, a fact that may partially explain their higher risk for COVID-related hospitalization and death. “We think it may be related to health-seeking behavior,” she said. “Patients often live alone and may not have support, may not seek out medical care very fast, and may not handle general medical problems very well.”

No funding source was indicated in the JAMA study.