Dozens of papers have examined the lingering mental health effects of COVID-19, but many have measured conditions such as depression and brain fog only a few months after infection. Now, a giant new study shows people who contracted COVID-19 faced substantially higher risks of neuropsychiatric ailments 1 year later, including brain fog, depression, and substance use disorders. The report, based on millions of people who used the U.S. Department of Veterans Affairs (VA) health system early in the pandemic, is published today in The BMJ.
“Most of us experienced some sort of mental distress during the pandemic, but this shows that people with COVID-19 had a much higher risk of mental health disorders than their contemporaries,” says senior author Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis and chief of research at the VA St. Louis Health Care system. “It’s a wake-up call.”
Other scientists praise the study’s size. “The scale of … this study sets [it] apart … as well as the quality of the statistical methods used,” says Alex Charney, a neuroscientist and psychiatrist at the Mount Sinai Health System.
But the paper has limitations, including that the study population was 71% to 76% white, 90% male, and on average 63 years old. “This is a Veterans Affairs cohort and not generalizable,” says Sung-Min Cho, a neurointensivist at Johns Hopkins University’s School of Medicine who is senior author on a new meta-analysis of the literature on neuropsychiatric manifestations of Long Covid.
The paper comes 1 week after Al-Aly’s group published a parallel study analyzing the same population, which reported that the risks of 20 heart and blood vessel ailments were significantly elevated in COVID-19 survivors after 1 year compared with their pandemic-era peers.
In the neuropsychiatric outcomes study, Al-Aly and colleagues analyzed the electronic health records of nearly 154,000 infected veterans and 5.8 million uninfected controls who used the VA health system in the first 10.5 months of the U.S. pandemic. (They also analyzed a historical control group of 5.9 million veterans who sought care in 2017.)
Because the researchers analyzed data from before vaccines were widely available, less than 1% of the veterans were vaccinated before they got COVID-19, so the analysis could not assess outcomes in vaccinated people who had breakthrough infections. (The authors have a separate paper under review that addresses that question.)
In the current analysis, the researchers found that 1 year later, survivors of COVID-19 were 46% more likely than pandemic-era controls to have been diagnosed with any of 14 neuropsychiatric disorders. These included depression, suicidal thoughts, anxiety, sleep disturbance, opioid use disorder, and neurocognitive decline or “brain fog.” The risk of brain fog was 80% higher than in controls, which translates to 10.75 more cases for every 1000 infected people. People hospitalized with coronavirus infections had the highest risk of developing any of the disorders—343% more than controls. Outpatients faced a 40% higher risk of developing an ailment.
Infected veterans were also 86% more likely to have received a prescription for an opioid, a benzodiazepine such as Valium, an antidepressant, or another neuropsychiatric drug.
Neuroimmunologist Cecilie Bay-Richter of Aarhus University notes that just how infection could damage mental health is unclear. She says animal studies will be needed “to be able to truly disentangle the direct, biological causes from the indirect causes” of long-term neuropsychiatric conditions.
For instance, the results could be skewed if COVID-19 survivors sought health care at higher rates than controls, an issue the authors acknowledge. “People recovering from COVID-19 might have a lower threshold for presenting for health care, or their doctors might be more likely to make a diagnosis,” says Paul Harrison, a psychiatrist and neuroscientist at the University of Oxford. Still, he added in comments made to the Science Media Centre: “The findings strengthen the case for adequate resourcing of mental health care in COVID-19 survivors.”