In April 2021, a multi-institutional team led by NYU Langone Health researchers published the first study to evaluate potential increased risk of death from SARS-CoV-2 infection in individuals with psychiatric diagnoses. The results, reported in JAMA Psychiatry, received widespread attention from policy makers and the scientific community.
“My suspicion is that we’re seeing an immune-mediated phenomenon. Schizophrenia is associated with low-grade inflammation, for example, and this may interfere with the immune system’s ability to mount a more targeted response to SARS-CoV-2 infection.”
Katlyn Nemani, MD
While the team had hypothesized that the risk of death would be highest for patients with schizophrenia spectrum disorders, the magnitude of that risk was unexpected—nearly three times that of patients without a psychiatric disorder. Other researchers soon replicated these findings, both in the United States and elsewhere.
Since publishing their initial research, lead author Katlyn Nemani, MD, a research assistant professor of psychiatry, and colleagues including senior author Donald C. Goff, MD, vice chair for research in the Department of Psychiatry, have been further investigating the causes of this striking disparity.
“My suspicion is that we’re seeing an immune-mediated phenomenon,” Dr. Nemani explains. “Schizophrenia is associated with low-grade inflammation, for example, and this may interfere with the immune system’s ability to mount a more targeted response to SARS-CoV-2 infection.”
An Increased Risk Revealed
In the initial study, the investigators analyzed EHRs of 7,348 adult COVID-19 patients in the NYU Langone Health system in New York City and on Long Island between March 3 and May 31, 2020. Of these, they identified 14 percent who were diagnosed with schizophrenia, mood disorders, or anxiety. They then calculated patient death rates within 45 days of testing positive for SARS-CoV-2. Risk of mortality was assessed after controlling for age, sex, race, and known medical risk factors.
Patients with schizophrenia proved to be by far the most vulnerable subgroup in the mental illness cohort. The team’s findings placed schizophrenia second only to age in strength of an association with mortality among all demographic and medical risk factors examined in the sample.
The CDC subsequently added schizophrenia and other mental health conditions to the list of comorbidities that increase the risk of severe COVID-19.
A New Insight: Antipsychotics and COVID-19 Risk
One crucial question following the initial study was whether psychiatric medications might play a role in raising schizophrenia patients’ odds of dying from COVID-19—a possibility suggested by population studies showing an association between heightened risk and prior antipsychotic use.
In a research letter published in September in JAMA Psychiatry, Drs. Nemani and Goff, along with other NYU Langone colleagues, reported new findings suggesting that this association may be related to underlying psychiatric diagnosis rather than its treatment.
They analyzed the EHRs of 464 COVID-19 patients who had been previously diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, 196 were treated with antipsychotics. The primary end point was death within 60 days of COVID-19 diagnosis.
Once again, adjusted risk of mortality was nearly threefold higher for patients in the schizophrenia spectrum group than for the reference population. However, mortality rates were equivalent in antipsychotic users and non-users.
Continuing to Seek an Explanation
Dr. Nemani continues to investigate the factors affecting COVID-19 outcomes in patients with schizophrenia. In a study currently in submission, she and her team looked at the association between specific antipsychotics and risk of SARS-CoV-2 infection. They found no antipsychotic medication that increased infection risk, and a few that decreased it.
She also plans to study how patients with schizophrenia respond to COVID-19 vaccines compared to healthy patients. “Some evidence suggests patients with schizophrenia have premature aging of the immune system,” she explains. “A decline in immune function may contribute to their vulnerability to severe infection. This may also lead to a diminished response to vaccines.”
“Research like this could have important implications for the prevention and treatment of COVID-19 in people with schizophrenia, affecting everything from the selection of antipsychotics for a given patient to the timing of booster doses.”
Donald C. Goff, MD
Adds Dr. Goff, “Research like this could have important implications for the prevention and treatment of COVID-19 in people with schizophrenia, affecting everything from the selection of antipsychotics for a given patient to the timing of booster doses. And it will advance our understanding of a mental disorder that’s associated with heightened risk of mortality even in the absence of a global pandemic.”
