The Emerging Links Between Covid-19 and Chronic Fatigue Syndrome

An illustration of a fatigued person, lying down on a bench and dreaming of a brighter day.
Illustration: Virginia Gabrielli

Almost everyone is familiar with the short-term symptoms of an acute SARS-CoV-2 infection. These include a fever, cough, breathing problems, fatigue, diarrhea, and other flu-like symptoms. While some doctors have raised alarms about the infection’s potential to inflict lasting organ damage, the popular perception of Covid-19 is that a small percentage of patients die and the rest recover.

But as the pandemic has stretched on, experts have begun to recognize that many Covid-19 patients — maybe even a majority — continue to grapple with a range of “post-viral” symptoms.

“Prolonged fatigue as well as brain fog and other persistent symptoms have been reported in a lot of Covid-19 patients.”

Some of these patients eventually get all the way back to normal, even if it takes a few weeks or months for that to happen. But some don’t. And for those who have yet to fully recover, there’s a growing suspicion that the virus may act as a catalyst for a condition that is commonly, if a bit misleadingly, known as chronic fatigue syndrome.

“Prolonged fatigue as well as brain fog and other persistent symptoms have been reported in a lot of Covid-19 patients,” says John Swartzberg, MD, an infectious disease expert and emeritus professor at the University of California, Berkeley. He says that these post-viral symptoms are typical of chronic fatigue syndrome, an illness that also goes by the name myalgic encephalomyelitis and is often abbreviated ME/CFS.

“We know that in patients who develop [ME/CFS], it’s often triggered by a bad viral infection,” he says. “And so there’s the thought that SARS-CoV-2 could be a cause.”

The relationship between Covid-19, ME/CFS, and ‘Post-Viral Syndrome’

In July, the Journal of the American Medical Association (JAMA) published a report from Italy that found that the bulk of former Covid-19 patients — those who had been hospitalized, discharged, and who no longer tested positive for the infection — continued to grapple with health issues months after their ostensible recovery.

Among the 143 people interviewed for the report, only 18 were symptom-free 60 days after their hospital discharge. More than half of the people interviewed said that they still experienced three or more symptoms, among which fatigue was the most common issue cited.

During a recent press conference, Anthony Fauci, MD, director of the U.S. National Institute of Allergy and Infectious Diseases, talked about the potential long-term effects of Covid-19 — and specifically whether people who develop the illness are at risk for chronic ailments. Fauci said that many Covid-19 patients report health issues that are “highly suggestive” of ME/CFS. “If you look anecdotally, there is no question that there are a considerable number of individuals who have post-viral syndrome that . . . can incapacitate them for weeks and weeks following so-called recovery and clearing of the virus,” Fauci said.

He mentioned brain fog, fatigue, and problems concentrating as some of the symptoms most often mentioned among recovering Covid-19 patients. Poor sleep, muscle pain, and depressive symptoms are some others. “This is something we really need to seriously look at,” he said. “There very well might be . . . a post-viral syndrome associated with Covid-19.”

Doctors have long recognized that viral infections can act as catalysts for fatigue, gut issues, and other health problems that persist long after the infection itself has gone. A 1987 report in the Journal of the Royal College of General Practitioners sketched the outlines of post-viral syndrome. “The syndrome typically follows an upper respiratory tract infection from which the sufferer fails to make a full recovery,” the author of that report wrote. The “cardinal symptom” is profound muscle fatigue, but poor memory, lack of concentration, and sleep disturbances are also common characteristics, the report states.

“We know that 80% of ME/CFS cases diagnosed in the past are attributed to some kind of infection, and typically it’s a viral infection.”

While doctors first identified and documented cases of ME/CFS more than 70 years ago, the disease was until recently considered “psychosomatic,” which some experts use as a polite euphemism for “imagined.” Fortunately, that’s changed. “I think it’s now widely accepted that there is a condition that causes profound and chronic fatigue in patients, and it’s not a psychosomatic disease,” UC-Berkeley’s Swartzberg says. “It seems to be common, but we don’t really know why it happens.”

To this day, few medical schools include ME/CFS in their curriculum, and most doctors and medical professionals are not trained to identify and treat the disease. “I would say that this is one of the most stigmatized illnesses,” says Leonard Jason, PhD, a professor of clinical psychology and an ME/CFS researcher at DePaul University in Chicago. “There are few experts in this field, and everything about it is controversial.”

Part of the problem, Jason says, is that there is currently no simple blood or lab test for ME/CFS. People who have it are usually diagnosed based on self-reported symptoms, although some recent work at Stanford University has identified potential biomarkers of ME/CFS. The CDC estimates that up to 2.5 million Americans have ME/CFS, but that 90% of those people have not been formally diagnosed.

One thing that experts do know: ME/CFS often follows a bout of infectious disease. “We know that 80% of ME/CFS cases diagnosed in the past are attributed to some kind of infection, and typically it’s a viral infection,” says Oved Amitay, CEO of the nonprofit Solve ME/CFS Initiative. He says that the Epstein-Barr virus, which causes mononucleosis (mono), is an established ME/CFS trigger. So are some of the older coronaviruses, including SARS and MERS.

He says that, from the very start of the SARS-CoV-2 outbreak, he and other members of his organization expected to hear reports of debilitating fatigue and other ME/CFS symptoms. “Unfortunately, none of this was surprising to us.”

How many people with Covid-19 could go on to develop ME/CFS? Jason says that some older research suggests that a significant percentage of people who develop viral infections — “We think maybe 10%, but it may be a larger percentage” — still feel ill six months later.

This six-month threshold is usually used to differentiate ME/CFS from the shorter-lived post-viral syndrome. But at this point, and especially when it comes to Covid-19, there are many more questions than answers.

The causes of post-viral syndrome and ME/CFS

Jason says that there are theories, but no hard-and-fast answers. “Some think that remnants of a virus might still be in a person’s system causing problems,” he says. While normal tests don’t reveal the continued presence of a virus, a component of it may still be secreted away in the brain or body, doing harm. “There are others that think the immune system gets revved up and does damage.”

The authors of a 2020 paper on post-viral syndrome among Covid-19 patients point out that the related SARS virus was known to cross the blood-brain barrier and trigger an improper inflammatory reaction that resembled the “disturbances” observed in ME-CFS patients.

The medical community’s interest in post-viral syndrome and ME/CFS has, up until recently, been minuscule. The novel coronavirus may change that.

The inflammation in the brain and hypothalamus could cause short-term symptoms like a fever, and also longer-term symptoms like a disturbed sleep-wake cycle, cognitive dysfunction, and exhaustion, they write.

Whatever is going wrong, Jason says he believes it’s ultimately something to do with the brain. “It’s the master organ, and we’re doing some work with brain neurons where we’re seeing some signs of dysfunction,” he says. “We think the immune system has the hit from the infection, and then it does the structural damage to the brain.” Some of his recent work on college students who have had mono and then gone on to develop ME/CFS suggests that certain immune system factors could predict who is at greater risk for the illness. But a lot more work needs to be done, he says.

As far as treatments go, he says most are targeted at specific symptoms — not at relieving or curing the disease. “Sometimes it’s just helping people with pain management,” he says. For those who experience exhaustion following physical activity, there are calibrated “pacing” guidelines that can help them avoid over-exerting themselves and exacerbating their condition. There are also some experimental drugs, though none is yet approved for the treatment of ME/CFS.

The bottom line, Jason says, is that the medical community’s interest in post-viral syndrome and ME/CFS has, up until recently, been minuscule. The novel coronavirus may change that.

“The field of ME/CFS has already changed dramatically in the last few months,” he says. “Before, there were quite a few people who would raise eyebrows, or patients who were treated pretty poorly.” Now that so many people are developing ME/CFS-like symptoms in the wake of Covid-19 illness, he says that most of the doubters have been silenced.

Solve ME/CFS Initiative’s Amitay says that it’s never been more vital for the medical science community and its public and private patrons to invest in ME/CFS research. “We have to study this now, because we believe this is a situation that will become a crisis if we don’t pay attention to it,” he says. “We know what we know, but there’s a lot that we don’t.”

I write about health and science. I live in Detroit with my wife and kids. I’m trying to learn German, but my progress so far is nicht gut.

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