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Twofold Increased Risk for Death From COVID-19 in Psych Patients

Patients with a mental illness, particularly a psychotic or mood disorder, are twice as likely to die after infection with SARS-CoV-2 compared with those without a psychiatric diagnosis, according to the results of the largest study of its kind to date.

These findings, investigators note, highlight the need to prioritize vaccination in patients with preexisting mental health disorders.

“We have proven beyond a shadow of a doubt that there are increased risks” among psychiatric patients who get COVID-19, study investigator Livia De Picker, MD, PhD, psychiatrist and postdoctoral researcher, University Psychiatric Hospital Campus Duffel and University of Antwerp, Belgium, told Medscape Medical News.

“Doctors need to look at these patients the same way they would other high-risk people, for example those with diabetes or chronic obstructive pulmonary disease,” all of whom should be protected against COVID-19, De Picker added.

The study was published online July 15 in Lancet Psychiatry.

Risk by Mental Illness Type

The systematic review included 33 studies from 22 countries that reported risk estimates for mortality, hospitalization, and ICU admission in patients with confirmed SARS-CoV-2 infection. The meta-analysis included 23 of these studies with a total of 1.47 million participants. Of these, 43,938 had a psychiatric disorder.

The primary outcome was mortality after COVID-19. Secondary outcomes included hospitalization and ICU admission after COVID-19. Researchers adjusted for age, sex, and other covariates.

Results showed the presence of any comorbid mental illness was associated with an increased risk for death after SARS-CoV-2 infection (odds ratio [OR] 2.00, 95% CI, 1.58 – 2.54; P < .0001).

When researchers stratified mortality risk by psychiatric disorder type, the most robust associations were for psychotic and mood disorders. Substance use disorders, intellectual disabilities, and developmental disorders were associated with higher mortality only in crude estimates. There was no increased death risk associated with anxiety disorders.

“That there are differences between the various types of disorders was an interesting finding,” said De Picker, adding that previous research “just lumped together all diagnostic categories.”

Potential Mechanisms

The study did not explore why psychiatric illness raise the risk for death in the setting of COVID-19, so potential mechanisms are purely speculative. However, the investigators believe it may reflect biological processes such as immune-inflammatory alterations.

Psychotic disorders and mood disorders in particular, are associated with immune changes, including immunogenetic abnormalities, raised cytokine concentrations, autoantibodies, acute-phase proteins, and aberrant counts of leukocyte cell types, said De Picker.

She likened this to elderly people being at increased risk following COVID-19 because their immune system is compromised and less able to fight infection.

There are likely other factors at play, said De Picker. These could include social isolation and lifestyle factors like poor diet, physical inactivity, high alcohol and tobacco use, and sleep disturbances.

In addition, psychiatric patients have a higher prevalence of comorbidities including diabetes, cardiovascular disease, and respiratory disease, which could also play a role.

The increased mortality might also reflect reduced access to care.

“Some of these patients may be living in difficult socioeconomic conditions,” said De Picker.

She noted that while the in-hospital mortality was not increased, the risk was significantly increased in samples that were outside of the hospital. This, she said, reinforces the need for providing close monitoring and early referral to hospital for psychiatric patients with COVID-19.

Mortality varied significantly among countries, with the lowest risk in Europe and the United States. This difference might be attributable to differences in healthcare systems and access to care, said De Picker.

Overall, the risk for hospitalization was about double for COVID patients with a mental illness, but when stratified by disorder, there was only a significantly increased risk for substance use and mood disorders. “But mood disorders were not even significant any more after adjusting for age, sex, and comorbid conditions, and we don’t see an increased risk for psychotic disorders whereas they had the highest mortality risks,” said De Picker.

Psych Meds a Risk Factor?

The studies were primarily based on electronic medical records, so investigators were unable to carry out “a fine grain analysis” into clinical factors affecting outcomes, she noted.

Antipsychotics were consistently associated with an increased risk for mortality (adjusted OR [aOR] 2.43; 95% CI, 1.81 – 3.25), as were anxiolytics (aOR, 1.47; 95% CI, 1.15 -1.88).

“There are some theoretical reasons why we believe there could be a risk associated with these drugs,” said De Picker. For example, antipsychotics can increase the risk for cardiac arrhythmias and thromboembolic events, and cause interactions with drugs used to treat COVID-19.

As for anxiolytics, especially benzodiazepines, these drugs are associated with respiratory risk and with all-cause mortality. “So you could imagine that someone who is infected with a respiratory virus and [is] then using these drugs on top of that would have a worse outcome,” said De Picker.

In contrast to antipsychotics and anxiolytics, antidepressants did not increase mortality risk.

De Picker noted a new study by French researchers showing a protective effect of certain serotonergic antidepressants on COVID outcomes, including mortality.

There was no robust evidence of an increased risk for ICU admission for patients with mental disorders. However, the authors noted some studies included small samples of patients with psychiatric disorders, “contributing to a low certainty of evidence for ICU admission.”

De Picker criticized COVID vaccine policies that don’t prioritize patients with psychiatric disorders. In many countries, groups that were initially green-lighted for the vaccine included healthcare workers, the elderly, and those with underlying conditions such as diabetes, obesity and even mild hypertension — but not mental illness, which is also an underlying risk, she said.

“Outstanding” Research

Commenting on the study for Medscape Medical News, Jonathan E. Alpert, MD, PhD, Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center, New York City, and chair of the American Psychiatric Association Council on Research, called it “outstanding” and the largest of its kind.

“There have been a number of studies that have come to similar conclusions, that people with psychiatric illness are at greater risk for poorer outcomes, but because any given study had a relatively limited sample, perhaps from one health system or one country, there were some inconsistencies,” said Alpert.

“This is the strongest report so far that has made the point that people with psychiatric illness are a vulnerable population for a negative outcome from COVID, including the most worrisome — mortality.”

The study helps drive home a “very important public health lesson” that applies to COVID-19 but goes “beyond,” said Alpert.

“As a society, we need to keep in mind that people with serious mental disorders are a vulnerable population for poorer outcomes in most general medical conditions,” he stressed, “whether it’s cancer or heart disease or diabetes, and special efforts need to be made to reach out to those populations.”

Alpert agreed that at the start of the pandemic, psychiatric patients in the US were not prioritized for vaccination, and although psychiatric patients may initially have found it difficult to navigate the healthcare system to learn where and how to get a COVID shot, today that barrier has mostly been removed, said Alpert.

“Our patients are at least as willing as any other subgroup to get the vaccine, and that includes people with psychotic disorders.”

The study was supported by the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry network and Fondazione Centro San Raffaele (Milan, Italy). De Picker reports grants from Boehringer Ingelheim and Janssen, outside the submitted work. She is a member of the European College of Neuropsychopharmacology Immuno-NeuroPsychiatry Thematic Working Group.

Lancet Psychiatry. Published online July 15, 2021. Full text

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