In the fall of 2009, one of us, Beth, was hit by an illness she suspects was H1N1 flu, which was circulating then. In 2012, the other, Brian, developed a sudden fever, which his doctors said was also likely of viral origin.
Neither of us recovered, and we’re both disabled to this day.
The long-term illnesses that can follow viral infections can be devastating — and are devastatingly common. In 2015, the nation’s top medical advisory body, the Institute of Medicine, estimated that between 800,000 and 2.5 million U.S. residents live with the illness or illnesses awkwardly named myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An estimated three-quarters of these cases were triggered by viral or bacterial infections.
Now, as a new pandemic virus is burning through the world and causing many deaths, researchers are raising alarms that the novel coronavirus and the COVID-19 disease it causes will also leave in its wake a potentially large population with post-viral problems that could be lifelong and, in some cases, disabling.
At the National Institutes of Health and elsewhere, scientists who have been studying post-viral ME/CFS are seizing the opportunity to focus on COVID-19 patients. They want to understand what biological factors separate those who regain their health from those who remain sick.
“We want to look at who recovers and who doesn’t,” said Avindra Nath, the head of clinical neurology at NIH’s Clinical Center in Bethesda, Maryland, who is gearing up to study COVID-19 patients. “It’s quite possible some will never get their health back.”
In addition to emerging reports of damage to lungs, kidneys and hearts, COVID-19 patients are complaining of ongoing crushing fatigue, muscle pain, cognitive problems and other symptoms that anyone with ME/CFS is very familiar with.
“I’m 69 days after my first symptoms and still feeling fatigued,” wrote Canadian comedian Wayne Jones on Twitter, saying he has tested positive for the new coronavirus. “I also have sore eyes, and weakness and headaches that come and go. All signs point to post-viral fatigue.”
Sometimes a precursor to ME/CFS post-viral fatigue syndrome can occur after virtually any viral infection. Symptoms wax and wane; a person can feel fine one day and terrible the next. Exercise or other usual activities can bring fever and often symptoms rushing back. Although there is no known treatment, these problems often resolve on their own.
But patients who have experienced post-viral fatigue syndrome advise the newly ill to rest, rest and rest some more, as returning to normal activities can trigger relapses. If symptoms continue for six months or longer, post-viral fatigue syndrome can convert to a diagnosis of ME/CFS, which is usually lifelong and often devastating. Up to 25% of ME/CFS patients are housebound or bedbound for years. There are no treatments approved by the Food and Drug Administration.
A survey organized by a group of COVID-19 patients called the Body Politic shows that many coronavirus symptoms overlap with those of post-viral fatigue syndrome. Fatigue, including severe fatigue, brain fog — problems with concentration and thinking — chills and sweats, and sleep problems were commonly reported among 640 respondents, who were recruited from online support groups. The Body Politic, which includes some patients with expertise in survey design and statistics, calculated that respondents had just a 20% chance of being symptom-free 50 days after the illness began. The group cautioned that while the survey suggests many respondents had long illnesses, the results may not apply to the broader population of COVID-19 patients.
The novel coronavirus is too new to say whether such lingering symptoms represent an extended COVID-19 illness or a post-viral syndrome. But researchers suspect at least some COVID-19 patients will remain sick and eventually develop post-viral ME/CFS. Their suspicions are grounded in previous research. Studies on other outbreaks — including those of Epstein-Barr virus, Ross River fever and Q fever — have shown that up to 12% of people who fell acutely ill never regained full health. Many were eventually diagnosed with ME/CFS.
After the first SARS epidemic, which sickened 8,000 people worldwide in 2002-2003, one study found that 27% of 369 survivors of that variety of coronavirus met the criteria for chronic fatigue syndrome several years later. If figures like this are seen with this novel coronavirus, SARS-CoV-2, which epidemiologists warn will eventually infect 50 to 70% of all U.S. residents, our nation is on track for a devastating wave of millions of patients with chronic post-viral illnesses.
“The most important study of several we’re starting is to get coronavirus-infected patients and follow them over time to see if they convert to ME/CFS,” said Ron Davis, a geneticist at Stanford University. His adult son, Whitney Dafoe, is seriously ill with the disease.
“If you point out the fact that you might not ever get over COVID-19, it’ll put people’s attention on this problem,” Davis said. “We need doctors to be reading COVID-19 information and be on the lookout for people who never get well. I think that’s extremely important.”
Stuck in an ‘on’ position
While it may sound odd that many different viruses can cause the same long-term problems, the answer is rooted in how the body defends itself. Viral infections trigger a common immune response, including fever and inflammation. Sometimes these defenses go awry, or get stuck in an “on” position even when the virus has been cleared, emerging research shows.
In 2017 and 2018, one of us, Brian, participated in an inpatient study at NIH searching for the biological basis of post-infectious ME/CFS. Over two visits, patients in the study undergo an extensive battery of medical testing. Now Nath and his team are adapting this study to follow post-COVID patients. The NIH hopes to bring COVID-19 survivors to NIH hospital in Bethesda this summer.
The NIH plans to study the immune systems of COVID-19 survivors, along with conducting exercise tests to spot problems with metabolism, and other tests to document any dysfunction in how the brain regulates heart rate and blood pressure. Problems in this area, the autonomic nervous system, are common in post-viral fatigue syndrome and ME/CFS.
Nath, a neurovirologist, has also performed autopsies on “about a dozen” patients, he said, who died of COVID-19. When conditions allow his laboratory to reopen, Nath plans to look for the coronavirus in the brains of these patients and to search for nervous system damage caused by the overwhelming inflammation that can accompany COVID-19. Researchers have published clues that sustained inflammation – including low-level inflammation in the brain – may be present in ME/CFS.
Reports already show that the novel coronavirus can, in rare cases, infiltrate the central nervous system. Some 30 COVID-19 patients in Italy have been diagnosed with Guillain-Barre Syndrome, hallmarked by rapid nerve damage that can lead to paralysis. In Detroit, one COVID-19 patient who died was reported to have extensive brain damage caused by his immune system’s overwhelming response to the coronavirus, a condition called hemorrhagic encephalopathy.
Research on ME/CFS, which was neglected for decades, has been gathering momentum in recent years. While federal funding remains low, ME/CFS researchers have documented brain dysfunction and extensive problems in the immune systems of patients. Emerging work has also highlighted damage to the body’s ability to produce energy, and some scientists think a literal lack of energy could lie at the heart of ME/CFS. Nath and other researchers plan to study energy production in COVID-19 survivors.
The NIH is also funding long-term research on a cohort of up to 2,000 COVID-19 patients who were hospitalized in the United States, said Joseph Breen, an immunologist at the National Institute of Allergy and Infectious Diseases. “Those people can be tracked,” Breen said. “If you do a longitudinal follow-on study correctly, it can really help understand the rate of ME/CFS and other problems that may be present. We’re going to learn things we never learned with SARS and MERS,” the two previous illnesses caused by different coronaviruses earlier this century.
One challenge, Breen said, is differentiating post-viral fatigue syndrome and ME/CFS from the lingering effects of being in an intensive care unit or on a ventilator, which are known risk factors for long-term ill health.
Speed the search for drugs
Mady Hornig, an immunologist at Columbia University’s Center for Infection and Immunity, said her group plans to follow COVID-19 patients with neurological symptoms, including loss of smell, to see who develops ME/CFS. She plans to recruit African American, Hispanic and American Indian patients, who are underrepresented in ME/CFS research. Hornig herself has had COVID-19 symptoms for six weeks, including a racing heart beat, which can signal issues with the autonomic nervous system.
At Stanford, Davis is partnering with the nonprofit Open Medicine Foundation. Already, clinics funded by the OMF are collecting blood from COVID-19 patients and asking them to wear activity tracking devices. “We want to study them at three months, six months, longer, and see who will be diagnosed with ME/CFS,” Davis said.
Hornig and Davis both say that watching COVID-19 patients could speed the search for drugs to reverse whatever goes awry in post-viral illnesses.
“Scientifically I think the most important thing to look at is . . . why they convert to ME/CFS. What’s different about them?” Davis says. “That could be extremely valuable, that could give us a valuable clue to . . . how to treat it.”
The personal and societal costs of ME/CFS are devastating. In 2015, the Institute of Medicine estimated a $24 billion annual U.S. burden in medical costs and lost productivity. For Beth, who was working as a product manager for a software company in San Francisco with a computer science degree from MIT, her lost earnings potential over the past decade can likely be measured in the millions of dollars. Instead of paying taxes on those lost wages, she is drawing monthly Social Security Disability Insurance. For Brian, the week before he became suddenly ill, he wrote a front-page story for The Washington Post, where he was a science writer, on a major advance in theoretical physics, the discovery of the Higgs boson. Six months later, his undiagnosed post-viral illness had gotten so bad he could not remember a four-digit number long enough to tap it into his phone.
Too many discussions of COVID-19 focus on the disease’s death rate while neglecting the risk of long-term health problems. Called morbidity, this measure of the burden of long-term disease is so important that the Centers for Disease Control and Prevention’s most read publication is “Morbidity and Mortality Weekly Report.” To effectively plan for a post-COVID future, the nation must fund long-term research on survivors and account for the morbidity associated with the novel coronavirus. Instead, there are states such as Pennsylvania categorizing every COVID-19 patient in its borders still alive after 30 days as “recovered.” That oversimplification will underestimate the true human and financial costs of the U.S. epidemic. Some COVID-19 patients with kidney damage will need expensive dialysis for a lifetime; some will have lung damage; others will be disabled by post-viral ME/CFS.
Given the historical neglect of ME/CFS — very few medical students even learn about it — many physicians and researchers who follow COVID-19 patients may think they’re discovering a new phenomenon in the patients who are slow to recover. Instead, they’ll be rediscovering a common illness that’s been known, and neglected and afflicting many people Speed the search for drugs
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Vastag was a science reporter at The Post from 2011 to 2014. Mazur is co-founder of #MEAction, a patient advocacy group. They are married and live in Hawaii.