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What Was an Unexpected Finding in COVID-19 Mortality Risk Factors?

  • Authors: News Author: Kelli Whitlock Burton; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 12/30/2021
  • Valid for credit through: 12/30/2022
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Target Audience and Goal Statement

This activity is intended for primary care physicians, psychiatrists, infectious disease specialists, nurses, pharmacists, and other clinicians who care for patients at risk for COVID-19.

The goal of this activity is to educate clinicians on recent study findings on psychiatric illness as a possible risk factor for mortality among patients with COVID-19.

Upon completion of this activity, participants will:

  • Assess any interaction between psychiatric illness and COVID-19
  • Analyze how psychiatric illness might affect the risk for mortality because of COVID-19
  • Outline implications for the healthcare team


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News Author

  • Kelli Whitlock Burton

    Freelance writer, Medscape


    Disclosure: Kelli Whitlock Burton has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Johnson & Johnson Pharmaceuticals Research & Development, L.L.C.

Editor/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

CME Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

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What Was an Unexpected Finding in COVID-19 Mortality Risk Factors?

Authors: News Author: Kelli Whitlock Burton; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 12/30/2021

Valid for credit through: 12/30/2022


Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

As we approach year 3 of the COVID-19 pandemic, there is increasing attention on the effects of COVID-19 on mental health. Research has suggested that COVID-19 is associated with worse mental health outcomes, but can preexisting psychiatric illness be a risk factor for COVID-19? Taquet and colleagues addressed this question, and the results of their study were published in the February 1 issue of The Lancet Psychiatry.[1]

Researchers queried a database with records from 54 US managed care organizations to evaluate the association between mental health and COVID-19. Nearly 20% (18.1%) of patients had a psychiatric diagnosis in the 14 to 90 days after COVID-19, including 5.8% of patients with a first psychiatric diagnosis. Compared with 6 other health events, such as influenza infection and cholelithiasis, COVID-19 was associated with a 1.6- to 2.1-fold increase in a first psychiatric diagnosis during the 14 to 90 days after the event. Researchers found significantly higher rates of anxiety, insomnia, and dementia after COVID-19.

In addition, preexisting psychiatric illness in the past year was associated with a relative risk of 1.65 (95% CI: 1.59, 1.71) for incident COVID-19; however, this research did not closely examine whether patients with psychiatric illness had worse outcomes of COVID-19. The current study by and colleagues addresses this issue.

Study Synopsis and Perspective

Schizophrenia and severe mood and anxiety disorders are associated with a significantly lower risk for COVID-19 but are tied to a 2- to 4-fold increased risk for 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 United States approaches 800,000.[2]

"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 November 1 in JAMA Network Open.[3]

Unexpected Finding

Researchers analyzed electronic health records for 2.5 million adults with private health insurance who were tested for SARS-CoV-2, the virus that causes 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 persons with anxiety disorder.

Despite their lower positivity rate, patients with schizophrenia had the highest odds for death from COVID-19 after adjusting for age, race, body mass index, and comorbidities (adjusted odds ratio [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 3 times as likely to die (aOR = 2.76 [95% CI: 2, 3.81]), and persons 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[4] 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, New York, New York, 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 after 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 is also possible that differences in mortality in the days after infection became attenuated over time.

Although a meta-analysis published in July and reported by Medscape Medical News at that time[5] 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.[6] 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.

Study Highlights

  • Investigators drew study data from a large US national healthcare database. Patients included in the study were adults who received a test for SARS-CoV-2 between February and December 2020.
  • Researchers assessed records to determine which patients had a prior diagnosis of schizophrenia, mood disorders, and anxiety disorders before SARS-CoV-2 testing.
  • Study analysis excluded patients who received psychotropic medications but who did not carry a diagnosis of psychiatric illness.
  • The main study outcomes were how psychiatric illness affected rate of positive testing for SARS-CoV-2 as well as the mortality rate of COVID-19 among those persons with the infection. The researchers defined mortality related to COVID-19 as death during COVID-19 hospitalization or within 7 days of the diagnosis of COVID-19.
  • The investigators adjusted the study results to account for demographic and disease variables, as well as smoking.
  • The study population included 2,535,098 patients. The mean age of patients was 44 ± 22 years, and 62% were female; 9% of patients were Black.
  • 1.23% of patients had a diagnosis of schizophrenia, and approximately 10% and 6% of the cohort had mood and anxiety disorders, respectively.
  • Characteristics in the cohort with psychiatric illness were significantly different compared with the control group without psychiatric illness. In particular, rates of smoking and most chronic illnesses were higher in the group with psychiatric illness.
  • The overall rate of positive testing for SARS-CoV-2 was 11.91%. Lower rates of positive tests were found among women, smokers, and for most chronic illnesses, with the exception of diabetes.
  • 31% of patients with schizophrenia received their SARS-CoV-2 test in an inpatient facility compared with just 12% of the control group.
  • The aOR for a positive SARS-CoV-2 test in comparing patients with schizophrenia vs control patients was 0.93 (95% CI: 0.87, 0.99). Patients with schizophrenia and mood disorders were less likely to test positive for COVID-19 compared with patients with anxiety disorders and control patients, possibly because of more social isolation among patients with schizophrenia and mood disorders.
  • The aOR for mortality for patients with schizophrenia vs the control group was 3.74 (95% CI: 2.66, 5.24). The respective aORs for COVID-19 mortality in the mood disorder and anxiety disorder groups were 2.76 (95% CI: 2, 3.81) and 2.34 (95% CI: 1.68, 3.27).

Clinical Implications

  • A previous study by Taquet and colleagues found higher rates psychiatric illness after COVID-19 compared with rates after 6 common health events. Preexisting psychiatric illness was also associated with a higher risk for incident COVID-19.
  • In the current study by Teixeira and colleagues, the presence of schizophrenia and mood disorders was associated with a lower risk for incident COVID-19, but mood disorders, anxiety disorders, and, particularly, schizophrenia were associated with higher risks for COVID-19 mortality.
  • Implications for the healthcare team: Psychiatric illness was an independent risk factor for COVID-19 mortality in the current study. The healthcare team should consider more aggressive treatment for patients with psychiatric illness and COVID-19.


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