As scientists around the world investigate why long COVID strikes some and not others, a new study finds that suffering psychological distress prior to COVID-19 infection may increase the chances of getting the lingering condition.
Researchers from the Harvard T.H. Chan School of Public Health in Boston said they were surprised at the strength of the association between long COVID and depression, anxiety, worry, perceived stress and loneliness.
But senior study author Andrea Roberts, a senior research scientist in the school's department of environmental health, said long COVID cases have reminded her of other physical health conditions that are associated with mental health, such as fibromyalgia or Lyme disease.
“We know from studies of people with depression and so forth that they have patterns of immune dysregulation, like inflammation in blood,” said Roberts. “We know from many other studies that your immune system is not as good at fighting off bacterial or viral infections when there's stress or depression."
To study the impact of mental health on COVID-19 infection, the researchers enrolled nearly 55,000 people in April 2020, just as the pandemic was unfolding, and asked them questions about their levels of psychological distress.
About 3,000 of the participants were infected with COVID-19 in the year that followed. The researchers asked them about their symptoms, then compared those who had long COVID to those who did not.
The team found that psychological distress was associated with a 32% to 46% increased risk of developing long COVID, and a 15% to 51% greater risk of daily life impairment.
An earlier study that Roberts was involved with showed that these same psychological factors were also associated with the risk of being hospitalized for COVID. COVID-19 severity is associated with long COVID, she noted.
A couple of hypotheses about long COVID are that the immune system is not clearing the virus as well as it is in people who don't have long COVID, or that fragments of the virus remain in a person's body and keep activating the immune system, Roberts said.
“What we don't know at this point is whether if you reduce people's stress or cure their depression, or treat their depression successfully, whether their risk will return to what it was before,” she explained.
Roberts said she is especially concerned about cases where the symptoms are causing significant impairment.
Losing your sense of smell or having a minor cough may not be debilitating, she said.
“But if you're so fatigued that you can't work, then that's a totally different order of magnitude,” Roberts said.
The U.S. Centers for Disease Control and Prevention estimates that 20% of American adults experience long COVID.
Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, said the findings jibe with prior research that showed having generalized anxiety disorder was a risk factor for developing long COVID.
“This signal, I think, is getting stronger, that there likely is some interaction with pre-existing psychiatric illness and long COVID,” Adalja said. “Right now, it's an association. There's a lot more work that needs to be done to tease out what the causal relationship would be, what the physiology might be for how that could occur.”
Many questions remain about why and in whom long COVID occurs, Adalja said. One issue is that it has “definitional problems,” in which some studies have lumped together cases that may also be post-ICU syndrome or post-hospital syndrome rather than long COVID alone, he noted.
Long COVID does seem to be more common in older people, in women and in those who have pre-existing conditions, including psychiatric issues, Adalja said. An association with reactivation of Epstein-Barr virus is also possible. Long COVID does seem to be less common in vaccinated individuals, he added.
Meanwhile bloodwork isn't finding inflammation in these long COVID patients, who may also test normally on echocardiography or lung function tests, Adalja said.
“The biggest question is actually understanding what's going on in the bodies of these individuals, what's the etiology of these symptoms and what relationship do they have with prior infection with COVID,” Adalja said. “All we have right now are some associations that might hint at understanding causes, but still not enough to be able to truly understand it.”
The findings were published online Sept. 7 in JAMA Psychiatry.
The U.S. Centers for Disease Control and Prevention has more on long COVID.
SOURCES: Andrea Roberts, PhD, MPH, senior research scientist, department of environmental health, Harvard T.H. Chan School of Public Health, Boston; Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security and adjunct assistant professor, Johns Hopkins Bloomberg School of Public Health and affiliate, Johns Hopkins Center for Global Health, and expert, Infectious Diseases Society of America, Baltimore; JAMA Psychiatry, Sept. 7, 2022, online