Schizophrenia Tied to Higher Risk of COVID-19 Death

People with schizophrenia may face a higher risk for severe COVID-19, a new study suggested.

Compared with COVID-19 patients without a psychiatric disorder, those previously diagnosed with schizophrenia spectrum disorder had more than a two times higher risk for mortality within 45 days of a confirmed case (odds ratio 2.67, 95% CI 1.48-4.80), reported Katlyn Nemani, MD, of New York University Langone Medical Center in New York, and colleagues.

This association was significant even after adjusting for medical risk factors including smoking status, hypertension, heart failure (HF), myocardial infarction, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, and cancer, they wrote in JAMA Psychiatry.

However, people with other mood disorders (OR 1.14, 95% CI 0.87-1.49) or anxiety disorders (OR 0.96, 95% CI 0.65-1.41) didn't see any increased risk of COVID-related mortality, according to the authors.

In a relative ranking of ORs for 18 different variables thought to be associated with an increased risk of COVID-19-related death, schizophrenia spectrum disorders was the highest ranked, and only behind age (45 years or older). Variables that trailed just behind schizophrenia as risk factors for mortality included being male, having HF, being a race other than White, having hypertension, being a current smoker, and having diabetes.

"We expected patients with psychiatric illness to be at higher risk for mortality in the setting of COVID-19 given their higher rates of medical conditions -- particularly cardiovascular disease. What came as a surprise was the high risk of mortality associated with schizophrenia spectrum disorders, which ranked only second behind age among all the demographic and medical risk factors we examined," Nemani told MedPage Today. "The magnitude of this finding after adjusting for other medical risk factors was unexpected."

She suggested two main explanations for this association: Possible risk tied to the medications used to treat schizophrenia spectrum disorders or abnormal immune response to infection associated with schizophrenia-spectrum illness.

"An association between severe infection and psychosis has been reported for decades, suggesting that the higher risk of death in patients with schizophrenia may not be unique to COVID-19," Nemani explained. "Some studies have suggested a higher risk of mortality from respiratory illness associated with some antipsychotic medications."

However, she pointed out that much of the data suggest that severe infections tend to come prior to a schizophrenia diagnosis, so use of antipsychotic medications can't fully explain this risk. On the other hand, people with schizophrenia may be less capable of mounting an appropriate immune response to infection, and they may be less efficient at fighting off viruses, as well as more prone to an uncontrolled inflammatory response, Nemani noted.

"It remains to be seen whether this abnormal immune response could contribute to increased risk of death from infections, including COVID-19, and the psychiatric symptoms that they experience," she stated.

This retrospective cohort analysis included 7,348 patients (mean age 54; 53% women; majority White) diagnosed with COVID-19 between March 3 and May 3, 2020 at the New York University Langone Health System at four acute care hospitals in Manhattan, Brooklyn, and Long Island.

Compared with 6,349 reference patients without a psychiatric disorder, 564 patients in the cohort had an existing mood disorder, 360 had an existing anxiety disorder, and 75 had an ICD-10 diagnosis of schizophrenia spectrum disorders.

Mortality was defined as death or hospital discharge to hospice within 45 days of COVID-19 diagnosis.

Study limitations included the fact that the accuracy of clinical psychiatric diagnoses could not be validated in all patients, and use of psychotropic medications at the time of the infection was not assessed. Also, people with psychiatric disorders may be less likely to seek medical attention, "particularly when there are systemic barriers to accessing care," the authors noted, although they stressed that all the patients in the current study had sought treatment previously.

Nemani told MedPage Today her group plans to conduct studies looking at both possible explanations for this relationship, including the abnormal immune response to infection and potential risk tied to the medications used to treat schizophrenia spectrum disorders.

"With this newfound understanding, health care providers can better prioritize vaccine distribution, testing, and medical care for this group," she said in a statement.

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