Long COVID and Mental Illness: How the brain can affect the body - Slate
Andrea Roberts was getting ready to submit a study for publication, and she was worried. A senior research scientist at the Harvard T. H. Chan School of Public Health, she had just written a paper suggesting that people with high stress levels were more likely to develop long COVID after an acute infection.
Roberts has spent the past decade studying the link between physical health and mental health. She knows that psychology can play a role in almost any illness; a few years ago, she discovered a link between PTSD and ovarian cancer. On paper, the new finding was no different from those in her previous studies, but this time she added a disclaimer to her article. "Our results should not be misinterpreted as supporting a hypothesis that post–COVID-19 conditions are psychosomatic," she wrote.
Her worries were not unfounded. The study was published in the Journal of the American Medical Association: Psychiatry on Sep. 7 of last year. A few days later, Jeremy Redfern, a member of Florida Gov. Ron DeSantis' administration, tweeted out the article and put "long COVID" in scare quotes. In the replies, people referred to long COVID as a "self-fulfilling prophecy" and "symptom of liberalism."
Roberts had meant to convey with the disclaimer that long COVID is not a fake condition, and that patients experiencing it are not duping doctors or themselves (as Redfern implied they were). In doing so, however, she used the word "psychosomatic" to mean "fake." But that's not how "psychosomatic" is used in medicine, and she now has mixed feelings about the disclaimer. "The actual definition of psychosomatic is a connection between your psyche and your soma," Roberts says—that is, your mind and your body. That connection can look like so-called "hysterical" blindness, where a traumatic experience causes someone to lose their sight without any apparent damage to their visual system, or like the well-known (and uncontroversial) relationship between stress and heart disease. Based on that technical definition, Roberts says what she's showing in the long COVID study "is actually psychosomatic."
No serious doctor would deny that the mind and body are intimately linked—many would even argue that it is meaningless to differentiate between the two, since the mind is really nothing more than the brain. But it wasn't just the right-wing Floridians looking to minimize long COVID who responded to her results. Pieces by mainstream journalists have suggested that linking depression and long COVID is tantamount to accusing all long COVID sufferers of being malingerers.
As of yet, there is no conclusive proof that stress or mental illness can contribute to long COVID. But since Roberts' paper, several other studies have found associations between post-COVID symptoms and mental illnesses like depression. None of this research proves that mental illness plays a role in causing long COVID—it might not play any direct role at all—but some experts see the connection as a promising path toward understanding, and treating, the condition. As long as the idea that mental illness is somehow less "real" than physical illness persists, however, investigating that link remains a risky proposition—both for the researchers, who might expose themselves to intense online criticism, and for the patients, who could see such studies weaponized against them.
"Being 'real' or not is a very false dichotomy," says Tracy Vannorsdall, associate professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins. "And it doesn't do our patients, or our scientific thinking, any good."
There's a great deal of work to be done before scientists know for sure whether mental illness contributes to long COVID. The studies to date are imperfect—many of them depend on electronic health records, which can give a skewed view of patients, especially given how often mental illnesses are misdiagnosed. And two illnesses can be statistically related without one causing the other.
Even if scientists do eventually discover that diseases like anxiety and depression can cause—or exacerbate—long COVID, that won't imply that one has to be mentally ill to develop the disease. Though the physical dimensions of long COVID are not fully understood, their presence in some people is incontrovertible: People with long COVID are more likely to have SARS-CoV-2 spike protein circulating in their bloodstreams after recovering from the acute phase of the illness, and they also tend to show differences in their immune systems.
But physical and psychological causes are not mutually exclusive. Long COVID may really be a collection of different illnesses, each of which comes about in its own particular way, and psychological factors might be more important in some of those illnesses than in others. And there is no reason why the physical and the mental couldn't both contribute. "I could have bad asthma, and I could have bad anxiety, and both could be contributing to my shortness of breath," says Adam Gaffney, a Harvard pulmonologist who has written about the possibility of psychological contributions to long COVID. "The fact that I have severe anxiety doesn't mean I don't also have asthma."
With these caveats in mind, many scientists and clinicians, including Gaffney, think the putative link between mental illness and long COVID is worthy of further investigation, both because of the studies that have come out so far and because the idea has what scientists call "face validity": It just makes sense. Mental illnesses like depression and anxiety are associated with a higher risk of heart disease, diabetes, and Alzheimer's, among numerous other conditions, and long COVID itself often involves psychiatric symptoms. And yet no one would propose that a heart attack survivor was faking their illness.
Medically speaking, there's nothing intrinsically surprising about those relationships. The physical underpinnings of conditions like depression remain obscure. But if everything, at bottom, is physical—and scientific practice insists that it is—then so too is depression, even if we don't yet understand how, exactly, it happens in the brain.
Mental illness is, however, sometimes treated as if it's less a disease of the body and more an affliction of the immaterial soul. "There's such a duality in how we think about mental health and physical health, as though one's real and one's not," says Via Strong, a psychologist at MedStar National Rehabilitation Hospital who works with long COVID patients. But "both are in your body, and both are real"—and if one shifts, so can the other.
From where the mind sits within your skull, it exerts a powerful influence over the rest of your body. The brain puppeteers the hormone system, which disseminates chemical signals through the bloodstream, and those chemicals can spark a wide variety of biological responses. In brief moments of upset, a rush of the hormone cortisol through the bloodstream can increase one's heart rate, slow digestion, and suppress the immune system. Basic bodily processes are put on pause; all available resources are devoted to the situation at hand.
In chronic stress, however, the brain commands the adrenal glands, a pair of conical organs that sit atop the kidneys, to release cortisol for far longer than they would typically. Over time, the hormonal system can start to malfunction, and the immune system goes haywire in response: Some immune cells stop working as effectively, and overall levels of inflammation may rise. The relationships here are complex—just as depression may cause inflammation, so too does inflammation raise one's risk of depression. But it's clear that depressed people tend to experience more inflammation, and inflammation may play a role in long COVID.
Akiko Iwasaki, a Yale immunologist, says she isn't yet convinced that mental illness can contribute to long COVID. If it does, however, she says that the tight interrelation between the body's hormonal and immune systems may offer a credible explanation. There is already some evidence of hormonal dysfunction in long COVID: In one study, Iwasaki and her colleagues found that long COVID patients had lower cortisol levels than healthy controls.
Mental illness wreaks its havoc on the body in indirect ways, too: It changes how people behave, from the quality of their sleep to the foods they choose to eat to the frequency of their social engagements. Michael Irwin, a professor of psychiatry at UCLA who studies the relationship between sleep and the immune system, thinks insomnia could potentially precipitate long COVID. He and his colleagues have found that people with insomnia tend to see their acute COVID symptoms linger longer, and two recent studies from other research groups have reported an association between sleep problems and long COVID.
This is hardly surprising. Irwin has helped establish that poor sleep can knock the immune system out of whack and trigger inflammation over the course of his decades-long career. And the link between stress and heart disease has been studied for more than half a century—baby boomers grew up hearing about the idea that emotional challenges can cause bodily changes.
Nor does any of it seem particularly controversial. Hormone levels and lack of sleep are so concrete—so indisputably real—as to make for dry reading. Jaime Seltzer, an advocate for people with chronic illnesses and the director of scientific and medical outreach for the organization ME Action, is generally skeptical of research on long COVID and mental illness. But she is willing to entertain discussions about the physical effects of depression and anxiety. "There are arguments that people can make for embodied reasons why this is happening, physiologically," she says.
If tying mental health to long COVID were merely a matter of measuring cortisol levels and sleep patterns, maybe it would be easy to get everyone on the same page. But though a general reluctance to talk about COVID and mental health might stymie researchers who want to study hormones and immune molecules, such research is at best peripheral to the core controversy. The real difficulties start to arise when we leave behind the body and focus fully on the brain.
When one of the first studies linking mental illness with long COVID risk was published in the Annals of Internal Medicine in 2022, Francesca Beaudoin, director of the Long COVID Initiative at the Brown University School of Public Health, penned a response cautioning readers not to make hasty assumptions about psychological causes. "Patients with [long COVID] already experience stigma and difficulty accessing care; our early work on [long COVID] should not exacerbate this," she wrote.
Beaudoin says her conversations with long COVID patients inspired her to write that response. "They felt 'gaslit' by the medical community, that they were being made to think that long COVID was in their heads, that it wasn't real and that they just needed to suck it up and move on," she says. She worried that the study would only reinforce that notion.
Long-haulers are not the first patients to feel gaslit and ignored. For a long time, ME/CFS—which is also known as chronic fatigue syndrome and bears a strong resemblance to some cases of long COVID—was popularly referred to as "yuppie flu." Some in the medical world also thought that the illness could have a social element: In 1970, two doctors published a paper in the British Medical Journal arguing that the condition, then referred to as "benign myalgic encephalomyelitis," was really mass hysteria.
In deploying the term "mass hysteria," the British doctors didn't mean to suggest that the patients were consciously faking their illness, but rather that their symptoms were purely psychological. But to many readers, the paper nevertheless seemed pejorative, and several clinicians and patients sent letters to the British Medical Journal expressing their indignation. "It is essential to treat this disease seriously," wrote Betty Scott, a doctor who had worked with myalgic encephalomyelitis patients. "If a diagnosis of 'hysteria' is even hinted, the patient experiences a profound loss of confidence in his medical advisers."
Today, many ME/CFS patients feel similarly about the idea that psychological factors may play a major role in their condition, and scientists have discovered a variety of biological changes in patients. That doesn't suggest that psychology is irrelevant, however. Patients are the experts on their own symptoms—but without medical examination, it can be impossible for them to tell whether those symptoms are rooted in biology, psychology, or both.
Someone who develops memory problems, for example, might assume that there's something wrong with their brain tissue—maybe it's inflamed, or maybe their neurons are dying. These explanations seem to match the often-disorienting experience of suddenly not being able to recall certain facts or struggling to formulate ideas. To many people, brain damage seems much more "real" than psychological issues like anxiety and depression. And memory difficulties can certainly arise from physical changes in brain tissue. But in some patients, cognitive difficulties represent a problem with the brain's software—the patterns of neuronal activity—rather than its hardware.
In her clinical practice, Vannorsdall, the Johns Hopkins professor, has encountered numerous patients—some with long COVID—who complain of memory problems in their daily lives, but score well on formal memory tests. Her observations are backed up by a recent study, which found that someone's likelihood of developing long COVID is correlated with their score on a self-reported survey of "perceived cognitive deficits" early in the illness course. Previous research has shown that those survey scores are unrelated to objective measures of cognitive functioning—but they are closely correlated with depression and anxiety.
These patients are experiencing genuine issues, even if they don't show up on clinical tests. Such memory loss can occur as a byproduct of mental illness. Someone with depression, for example, might start losing things more frequently because their inward rumination makes it difficult to focus on anything going on in the outside world. This shift can feel as real as a physical change—because it is real.
The mind can even radically alter how someone experiences their own body. Tell a patient you are giving them a drug and they might start to feel better, even if they've only taken a sugar pill; tell them the drug has side effects, and they may experience those, too.
Ultimately, psychology is just a different way of looking at biology. Even though the brain is a physical object, we have to describe some of the things it does—say, emotions—in psychological terms. Painstakingly cataloging the associated patterns of neuronal activity is simply beyond the reach of contemporary neuroscience.
Perhaps the greatest testament to the mind's astonishing power is the existence of functional neurological disorder (FND), a highly stigmatized condition in which people experience physical symptoms in the absence of any apparent biological cause. Patients with FND aren't simply imagining their condition, nor can they wish it away: What's going on in their brain is outside of their control. And the symptoms it causes can be severe. A substantial fraction of patients with seizures have FND, not epilepsy, and the lack of obvious abnormalities in their brains doesn't make their symptoms any less debilitating.
Contrary to popular perception, FND isn't just a catch-all bucket used to contain patients with poorly understood diseases. There are specific clues that doctors can use to identify FND, not unlike the mismatch between test performance and reported memory problems that Vannorsdall has seen in some of her patients.
But given the history of using psychology as a scapegoat for perplexing symptoms, it's unsurprising that some of the fiercest long COVID controversy has centered on FND. David Putrino, director of rehabilitation innovation for the Mount Sinai Health System and a long COVID researcher, describes people who endorse the comparison between long COVID and FND as "fringe scientists" and "fringe clinicians." And a recent article in the New Republic proposing that some cases of long COVID might qualify as FND sparked so much controversy that over 200 people signed a petition calling for extensive corrections to the article. ("We very carefully reviewed the concerns raised in the petition with our fact-checking department, and we found that none of the listed objections merited correction," said Michael Tomasky, the editor of the New Republic.)
Some of that controversy is rooted in fear, and understandably so. Long COVID patients fear not only that their doctors might ignore their complaints and that their friends might secretly believe they are crazy, but also that scientists might fail to cure their disease, if they thoughtlessly assume all long COVID is really just FND, or is rooted in mental illness in some other way. "It's undisprovable," Seltzer says.
Because the biology of mental illness remains poorly understood, and because there are so many mechanisms by which psychological difficulties could produce physical symptoms, it would be extremely difficult to demonstrate that depression and anxiety play no role in long COVID. But because there are specific signs and symptoms of FND, it is possible to test the more specific hypothesis that FND and long COVID are linked. Doing so might make sense. Strong, who has worked extensively with both FND and long COVID patients, says that some of her long COVID patients likely do qualify as having FND, though many do not—after all, long COVID likely comprises several different pathologies. And if some long COVID patients do turn out to have FND, that knowledge could help clinicians choose effective treatment strategies, like psychotherapy rather than, say, drugs.
Yet a recent review failed to find any studies on long COVID and FND. "The hypothesis that long COVID might in part correspond to a functional disorder remains untested," the authors wrote.
Long COVID symptoms are real, regardless of whether they derive partly from psychological factors, are connected to a hormonal stress response, or have nothing to do with mental health at all. But you wouldn't know that from the way people talk. "There's an implicit, long-standing hierarchy in the way we legitimize human suffering," Gaffney says. That hierarchy isn't just evident in the excision of psychology from the long COVID discourse—it also privileges more biological-sounding explanations, like those involving hormones, above those more grounded in the mind (though the mind itself is, of course, biological).
In the reluctance of many people to talk about long COVID and mental health, Gaffney sees an implicit endorsement of the idea that mental illness is fundamentally different from, and less real than, physical illnesses. Nothing so clearly crystallizes that stigma than the abiding falsehood that people with mental illness—or physical symptoms that derive from mental illness—can cure themselves if they just put their mind to it. It's an absurd idea on its face: Treating mental illness is notoriously difficult, and many people try numerous psychiatric medications before they find one that works, if they find it at all.
People like Seltzer are understandably wary of being folded into that category—accused of having some moral failing rather than a genuine illness. Seltzer doesn't think she is stigmatizing mental illness by opposing research on psychological causes of long COVID. Rather, she says, people with conditions like ME/CFS and long COVID are simply trying to defend themselves against the stigmatizing beliefs held by others. "Our culture stigmatizes mental illness, and this is being deliberately leveraged in a disease where there is not very good evidence of a mental health connection," she says.
Vannorsdall disagrees with Seltzer's assessment. Besides female sex, she says, anxiety and depression are some of the strongest risk factors that have been discovered to date. That might be down to anodyne hormonal factors, it could look more like FND, or perhaps some mysterious third factor contributes to both mental illness and long COVID and causes their association. Without further research, it's simply impossible to discern what lies beneath the observed link between long COVID and mental illness.
That's par for the course for science: Discover something mysterious, consider the possible explanations, and design studies to test them. But in such a charged environment, such research is a dicey proposition. Putrino rejects research into long COVID and FND on its face, but he's also uncomfortable with studies that examine long COVID and mental illness more generally. Even a study grounded in the most concrete details of depression's biology, he contends, has the potential to be misused. "We never conduct research in a vacuum," he says. According to him, it's poor scientific practice to ignore how people might leverage your research once it's out in the world.
Funding, too, can be divisive. Scientists won't be able to clarify the connection between long COVID and mental health with just a few well-designed studies. "There's not just one thing that is contributing to this, but there's really a constellation of factors, and many of those factors are all interrelated," Irwin says. "There's no straight pathway." Unknotting this complex tangle of factors will take lots of time and money—Irwin says that scientists' best shot is probably a longitudinal study that follows a large group of people over time, regularly taking physiological and psychological measurements and observing who develops long COVID.
Such long-term studies, however, are famously expensive. Though organizations like the NIH have committed substantial funds to long COVID research, the available coffers are not bottomless, and conducting one expensive study can mean giving up on another. With ME/CFS, Seltzer says, theories about psychological causes became a "sink" for research funding without offering much benefit to patients, and she worries about that pattern recurring with long COVID.
The researchers share that concern. "I think it's a little bit dangerous to be assigning the blame to mental health as a cause of long COVID, because then that takes away from the efforts of people like myself, trying to understand the root cause of this disease," says Iwasaki.
Right now, however, the role of mental illness may be going understudied. The various papers that have looked into a mental illness link represent only an infinitesimal fraction of the long COVID research, and some issues, like long COVID and FND, haven't been studied at all. But mental illness research is no distraction—rather, it could prove a route to treating some patients. If psychological factors have a considerable role to play in generating and maintaining long COVID symptoms, then psychological treatments should be studied just as rigorously as drugs like Paxlovid.
Already, mental health care is central to long COVID care: Living with long COVID can be psychologically taxing, and COVID itself may be able to spark mental illness by infiltrating the brain. And there's also a possibility that psychological treatment could alleviate long COVID symptoms more broadly. In a recent trial, around 60 percent of long COVID patients recovered from severe fatigue after a four-month course of cognitive behavioral therapy, compared to about a quarter of those who did not receive CBT. Patients on CBT also saw a significant improvement in their bodily symptoms, like pain and dizziness.
If mental illness can contribute to long COVID, that's all the more reason to pursue psychological treatments—and understanding exactly how that connection works could help clinicians target those treatments more effectively. "That's really where we need to start," Vannorsdall says. "It's really about getting people back to feeling good with the tools that we have available, and appreciating that if mental health tools are part of that package, it doesn't invalidate the realness of their experience and of their illness."
State of Mind is a partnership of Slate and Arizona State University that offers a practical look at our mental health system—and how to make it better.
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