Schizophrenia: A risk factor for COVID-19 mortality?

Individuals with a history of schizophrenia spectrum disorder may have an elevated risk of COVID-19–related mortality, according to a retrospective cohort study from the US. However, the increased mortality risk did not apply to patients with anxiety or mood disorders.

“Individuals with schizophrenia spectrum disorders had 2.7 times the odds of dying after adjustment for known risk factors,” said the investigators.

Study participants were 7,348 adults (mean age 54 years, 53 percent female) with laboratory-confirmed diagnosis of COVID-19 between March 3 and May 31, 2020, in the New York University (NYU) Langone Health System, New York, US, who were followed for 45 days. Based on electronic medical records, 1 percent (n=75) had a history* of schizophrenia spectrum disorder, 7.7 percent (n=564) had a history of a mood disorder, and 4.9 percent (n=360) had a history of an anxiety disorder.

A total of 864 patients died or were discharged to hospice within 45 days of the positive SARS-CoV-2 test result (11.8 percent).

After adjusting for age, sex, race, and medical risk factors, compared with patients without psychiatric disorders (control group)**, patients with a history of schizophrenia spectrum disorder had a more than twofold risk of COVID-19–related mortality*** within 45 days of a positive SARS-CoV-2 test (adjusted odds ratio [adjOR], 2.67, 95 percent confidence interval [CI], 1.48–4.80). [JAMA Psychiatry 2021;doi:10.1001/jamapsychiatry.2020.4442]

Conversely, patients with a history of mood disorder did not have an increased risk of COVID-19–related mortality compared with patients without psychiatric disorders (adjOR, 1.14, 95 percent CI, 0.87–1.49), nor did those with a history of anxiety disorder (adjOR, 0.96, 95 percent CI, 0.65–1.41).

In a secondary analysis of patients with a recent diagnosis of psychiatric disorder (between January 1, 2019 and March 3, 2020), schizophrenia spectrum disorder was associated with an increased risk of 45-day COVID-19–related mortality (OR, 2.67). Mood disorders were also associated with an increased mortality risk after adjustment for demographics (OR, 1.52) but this was no longer significant following adjustment for medical disorders (OR, 1.27).

“[This increased mortality risk with a recent diagnosis of a psychiatric disorder suggests] that stage of illness (acute vs stable) may contribute to differential risk in patients with episodic psychiatric disorders,” said the investigators.

They highlighted that schizophrenia spectrum disorder was the second biggest risk factor for COVID-19–related mortality behind age (ORs, 35.72, 16.54, 7.74, and 3.89 for ages ≥75, 65–74, 55–64, and 45–54 years, respectively).

A high-risk group

“Identification of risk factors associated with poor [COVID-19] outcomes is important to guide clinical decision-making, target enhanced protective measures, and allocate limited resources,” the investigators pointed out.

“Our findings illustrate that people with schizophrenia are extremely vulnerable to the effects of COVID-19,” said lead author Assistant Professor Katlyn Nemani from NYU Langone Medical Center, New York, New York, US. “With this newfound understanding, healthcare providers can better prioritize vaccine distribution, testing, and medical care for this group,” she said.

As to the mechanism behind the association, biological factors related to schizophrenia spectrum disorder may play a role in the increased mortality risk, in addition to “systemic barriers to care and delayed treatment,” said the investigators. “[I]mmune dysregulation in the setting of genetic or acquired risk factors is a possibility,” they added.

“Now that we have a better understanding of the disease, we can more deeply examine what, if any, immune system problems might contribute to the high death rates seen in these patients with schizophrenia,” said senior author Professor Donald Goff, also from NYU Langone.

The investigators cautioned that the findings may not extend to other patient populations and that the influence of psychotropic medications on the clinical outcomes was not known.