St. Louis—So-called "long COVID" might not just involve physical symptoms. A new study suggests that patients who survive COVID-19 are at higher risk of mental health disorders—in some cases, even if they were not hospitalized.

The largest increases were in new anxiety, depressive, and stress/adjustment disorders, according to the report in The BMJ. Of specific concern to pharmacists, those patients also demonstrated higher use of antidepressants and benzodiazepines.

"The findings suggest that people who survive the acute phase of COVID-19 are at increased risk of an array of incident mental health disorders," wrote the authors from St. Louis University, Washington University School of Medicine, and the Veterans' Affairs (VA) St. Louis Healthcare System. "Tackling mental health disorders among survivors of COVID-19 should be a priority."

The study team used a cohort study to estimate the risks of incident mental health disorders in survivors of the acute phase of COVID-19.

Participants were veterans receiving care at the VA. Researchers created a cohort with 153,848 recovered patients who survived the first 30 days of SARS-CoV-2 infection and two control groups: a 5.6 million–member contemporary group with no evidence of SARS-CoV-2 and a 5.9 million–member historical control group that predated the COVID-19 pandemic.

Results indicated that the COVID-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 [95% CI 1.30-1.39]); risk difference 11.06 (95% CI 9.64-12.53 per 1,000 people at 1 year), depressive disorders (1.39 [1.34-1.43]; 15.12 [13.38-16.91] per 1,000 people at 1 year), and stress/adjustment disorders (1.38 [1.34-1.43]; 13.29 [11.71-14.92] per 1,000 people at 1 year).

The authors also reported an increase in that group of use of antidepressants (1.55 [1.50-1.60]; 21.59 [19.63-3.60] per 1,000 people at 1 year) and benzodiazepines (1.65 [1.58-1.72]; 10.46 [9.37-11.61] per 1,000 people at 1 year). In addition, the risk of incident opioid prescriptions also increased (1.76 [1.71-1.81]; 35.90 [33.61-38.25] per 1,000 people at 1 year), as did opioid use disorders (1.34 [1.21-1.48]; 0.96 [0.59-1.37] per 1,000 people at 1 year) and other (nonopioid) substance use disorders (1.20 [1.15-1.26]; 4.34 [3.22-5.51] per 1,000 people at 1 year).

Incident neurocognitive decline (1.80 [1.72-1.89]; 10.75 [9.65-11.91] per 1,000 people at 1 year) and sleep disorders (1.41 [1.38-1.45]; 23.80 [21.65-26.00] per 1,000 people at 1 year) also were amplified in the COVID-19 group.

The risk of any incident mental health diagnosis or prescription was increased (1.60 [1.55-1.66]; 64.38 [58.90-70.01] per 1,000 people at 1 year), the researchers pointed out.

That effect occurred even among people who were not admitted to hospitals, although the highest rates were among those who had been inpatients during the acute phase of COVID-19.

"Results were consistent with those in the historical control group," researchers noted. "The risk of incident mental health disorders was consistently higher in the COVID-19 group in comparisons of people with COVID-19 not admitted to the hospital versus those not admitted to hospital for seasonal influenza, admitted to hospital with COVID-19 versus admitted to hospital with seasonal influenza, and admitted to hospital with COVID-19 versus admitted to hospital for any other cause."

Corresponding author Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center, Research and Development Service at the VA Saint Louis Health Care System, points out in a linked opinion piece, "Altogether, the findings suggest that people with COVID-19 are experiencing increased rates of mental health outcomes, which could have far-reaching consequences. The increased risk of opioid use is of particular concern, especially considering the high rates of opioid use disorders pre-pandemic. The increased risks of mental health outcomes in people with COVID-19 demands greater attention now to mitigate much more serious downstream consequences in the future."

Dr. Al-Aly cautioned that the study's findings might be used to "gaslight or dismiss long COVID as a psychosomatic condition or explain the myriad manifestations of long COVID as the result of mental illness" but also responded, "This dismissal is contrary to scientific evidence and is harmful to patients and communities. Mental health disorders represent one part of the multifaceted nature of long covid which can affect nearly every organ system (including the brain, heart, and kidneys). Our results should be used to promote awareness of this risk among people with COVID-19 and to guide efforts for the early identification and treatment of affected individuals."

He recommended that thinking about SARS-CoV-2 be "reframed." While generally considered a respiratory virus, Dr. Al-Aly argues that it is "a systemic virus that may provoke damage and clinical consequences in nearly every organ system—including mental health disorders and neurocognitive decline."

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