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Unexpected Finding COVID Mortality Risk Factors

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Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk of COVID-19 but are tied to a two- to fourfold increased risk of death from the virus, new research shows.

The study results held after controlling for other risk factors and contradict an earlier study that showed no increased mortality risk associated with mood or anxiety disorders. The findings come as the overall number of deaths in the US approaches 800,000.

“These patients were less likely to be infected because they were probably less exposed, but once they have the infection, they are more prone to worse outcomes,” lead author Antonio L. Teixeira, MD, PhD, professor of psychiatry with McGovern Medical School at the University of Texas Health Science Center at Houston, told Medscape Medical News.

The study was published online November 23 in JAMA Network Open.

Unexpected Finding

Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for COVID-19 in 2020.

The overall positivity rate for the entire cohort was 11.91%, and patients with severe psychiatric illness fell below that rate. Positivity rates were 9.86% for people with schizophrenia or mood disorders and 11.17% among those with anxiety disorder.

Despite their lower positivity rate, patients with schizophrenia had the highest odds of death from COVID-19 after adjusting for age, race, body mass index, and comorbidities (aOR, 3.74; 95% CI, 2.66 – 5.24).

Those results were not very surprising, Teixeira said, as earlier studies have reported similar findings. However, the data on individuals with mood and anxiety disorders were unexpected.

Patients with mood disorders were nearly three times as likely to die (aOR, 2.76; 95% CI, 2.00 – 3.81), and those with anxiety disorders had more than double the mortality risk (aOR, 2.34; 95% CI, 1.68 – 3.27).

“We were expecting some increase, but there was strong evidence in those populations as well,” he said. “We were especially surprised at the data on patients with anxiety disorders.”

An Outstanding Question

These findings contradict a January 2021 study that showed no significant increase in mortality risk among those with mood or anxiety disorders.

Study methodology and timing might explain some of the differences, Katlyn Nemani, MD, a research assistant professor of psychiatry at the New York University Grossman School of Medicine, who led that earlier study, told Medscape Medical News.

Nemani’s study had a smaller study sample, examined mortality over a 30-day period after a positive COVID-19 test, and was limited to the peak of the pandemic in New York, between March and May 2020. Teixeira’s team examined a full year of data and assessed mortality for 7 days following a positive test.

“It is possible patients with some psychiatric disorders were less likely to receive or successfully respond to treatment for severe COVD-19 which evolved during the course of the pandemic,” Nemani said, adding that it’s also possible that differences in mortality in the days following infection became attenuated over time.

While a meta-analysis published in July and reported by Medscape Medical News at that time did show higher COVID-19 mortality among patients with mood disorders, the risk was far lower than that reported in this new study. That report, which included 33 studies in 22 countries, also found no increase in risk among those with anxiety disorder.

In October, the Centers for Disease Control and Prevention added mood disorders to the list of medical conditions that increase the risk for more severe COVID-19. Schizophrenia was already on that list.

“The outstanding question is what underlies this increased risk,” Nemani said. “Future studies focused on immune-mediated mechanisms and other potential explanations will help guide targeted interventions to reduce morbidity and mortality in this vulnerable population.”

Funding for the study was not disclosed. Teixeira and Nemani report no conflicts of interest.

JAMA Netw Open. Published online November 23, 2021. Full text

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