As the coronavirus grew from a fleeting concern to a full-blown panic, Lili Lim started to hear about people for whom the illness lasted weeks or even months. There were news stories of young people who couldn’t shake their fatigue or cognitive malaise, of folks who had to quit their job due to debilitating exhaustion.
For Lim, the symptoms were frighteningly recognizable.
“We would see them and say that these people are exactly like us,” said the 27-year-old, who was diagnosed with myalgic encephalomyelitis (ME) – also known as chronic fatigue syndrome (CFS) – in 2018. Lim is a patient-advocate within the ME/CFS community and was quick to relate to the plight of those with long Covid. “This is the same thing, it’s just happening with a different virus.”
Chronic fatigue syndrome and long Covid are both part of a much larger group of illnesses that arise after a viral, or sometimes bacterial, infection. Mononucleosis, HIV, Lyme, Ebola, Sars and many other infections can also have similarly prolonged effects. But experts say attention, funding and research into these post-infectious illnesses has historically been limited, and patients have often had their symptoms minimized or dismissed.
Long Covid has changed that. While millions of people across the world were already living with post-viral illnesses before the pandemic, a 2021 study published by the American Medical Association found that more than half of Covid patients reported symptoms lasting longer than six months. That means that the pool of potential post-viral illness patients has probably grown many times over during the pandemic. The surge has left scientists scrambling to find answers and unlocking the mysteries of persistent Covid, they say, could translate to further understanding of other post-infectious afflictions as well.
“This is one of the silver linings,” said Ziyad Al-Aly, director of the clinical epidemiology center at Washington University in Saint Louis.
Perhaps the most notable effort to understand long Covid is spearheaded by the US National Institutes of Health (NIH), which has allocated some $1.15bn to the Researching Covid to Enhance Recovery (Recover) project. And one of its taskforces explicitly aims to track the similarities between long Covid, ME/CFS and other post-viral conditions.
“It is a massive increase in funding,” said Leonard Jason, a psychologist at DePaul University who has spent decades researching post-viral illnesses. By comparison, the NIH has explicitly allotted only $35m to ME/CFS research over the next five years. “How many research areas do you go into where you have to convince people it’s a legitimate area of study? That all changed two years ago.”
Historically, scientists have focused on the more immediate impacts of a virus rather than its lingering tail. “We as doctors pretty much ignored the post-viral illness for the last 100 years,” said Al-Aly. “We didn’t really study it, we didn’t really track it over time.”
The 1918 flu was linked at the time to what was called encephalitis lethargica, or “sleepy sickness” (though no connection has ever been formally established), and similar symptoms arose during the more minor 1957 and 1963 influenzas. But in each of those instances there was little if any research done to link the long-term effects to the virus. Post-polio syndrome is another illness that received limited attention, especially after a vaccine for the virus became widely available in the 1950s. Sars, Ebola and other more recent outbreaks have also led to lasting effects, though not at case numbers high enough to spur extensive study.
ME/CFS has been perhaps the most common post-viral diagnosis over the last few decades, with a pre-pandemic estimate of about 1.5m cases in the US. But even those patients have found it difficult to be heard.
Billy Hanlon, 33, has been living with ME/CFS for about five years now. But, at first, doctors either attributed his symptoms to a psychosomatic illness, or dismissed them all together. “It was a pretty jarring experience to realize that you aren’t taken seriously,” he recalled. It wasn’t until he traveled to a specialist in North California that he finally received a diagnosis. . “I was putting all my effort into work and running around to the appointments,” he said. Eventually, the illness forced him to quit his job.
Lim said she also had trouble getting people to take her seriously, despite severe symptoms. “I was basically at home for three years,” she explained. “I couldn’t work. I couldn’t really see people. It was hard to even convince my family this was real.”
Such stories are all too common, said Jason, who has seen countless such instances. But the sheer scale of long Covid could change how the medical community handles post-viral illnesses. “That’s an enormous number of people. It’s crying out for something to be done,” he said. “If we can better understand the nature of these types of unexplained illness we will ultimately have a transformation of the healthcare system.”
Scientists are the first to admit how much they still have much to learn about post-viral illnesses. Jerry Krishnan, a professor of medicine and public health at the University of Chicago Illinois, is among those who have shifted his focus to long Covid and he breaks his curiosity into three general categories: the virus itself, the patient response to the virus and the social or biological determinants of what leads to the prolonged illness.
All of those areas, he said, will require more basic research. “If you can’t describe the problem, you can’t solve the problem,” he said, adding: “We have to move from descriptive work to understanding the biology.”
Krishnan, who helps spearhead the Recover program’s work in Illinois, said the massive influx of long Covid funding had already helped jumpstart that baseline science. Recover researchers are, for instance, currently in the midst of a $470m nationwide population study of long Covid. Work like that, Krishnan said, is “the only way” to begin treating or even preventing post-viral illnesses.
Joanna Hellmuth agrees. She’s a neurologist at the University of California San Francisco Memory and Aging Center, and before the pandemic she studied the long-term cognitive impacts of HIV – such as motor, memory or mood problems. Despite years of research, Hellmuth said scientists still “don’t really know why this is happening”.
But she doesn’t see funding as the only impediment to progress, and also points to a historical dearth of people working on post-viral illness. When she first started, she remembered, “I was even told by other neurologists that it was a bad choice of career.”
Long Covid has upended that notion, she said, and galvanized the scientific community. “I’ve gotten emails from people in all kinds of disciplines,” said Hellmuth. “There are so many people interested in this problem.”
Hellmuth also stresses the need for more baseline science, such as better understanding how viruses travel and stay in the body. With HIV, for example, Hellmuth said the virus moves to the brain where it probably creates tiny reservoirs that could make the illnesses particularly intractable. “We’re hoping that we can identify similar mechanisms,” she said of other viruses, “and hopefully develop not only treatments but also prevention.”
It’s too soon to say exactly what treatments for post-viral illness might look like. Perhaps more antivirals, or maybe steroids, said Krishnan. Monoclonal antibodies is another possible option, among many. Sorting through the science for solutions will take time and resources, he said. And treatments will also probably be not just virus-dependent but person-specific. “This is going to ultimately come down to personalized treatment,” said Krishnan.
But researchers seem particularly excited about the possibility that these post-viral illnesses could be predicted, mitigated or maybe even prevented before serious onset. Jason, at DePaul, has already started to identify risk patterns in his research. One recent study of college students who got mononucleosis found that pre-existing immune system deficiencies were a very strong indicator of which patients went on to develop ME/CFS.
“We could predict with over 95% accuracy who would recover or who wouldn’t,” said Jason.
Such information could allow doctors to better protect or prioritize vulnerable populations. But, he added, that still leaves the more basic questions of what’s causing these lingering maladies and what more can be done to help patients.
While the unprecedented scientific push for those answers continues, Jason is heartened to see that long Covid has already brought at least some social progress for post-viral patients. “People are less likely to say there’s nothing wrong with you,” he said. “They’re going to have a little bit less stigma, and that’s a good thing.”
Lili Lim has felt that shift as well. She’s allowing herself to be hopeful. “I loved weightlifting, swimming, teaching basketball,” reminisced the former athlete. “If I could regain the ability to exercise, I would be the happiest person in the world.”
This article was amended on 17 October 2022 to correct the state where Billy Hanlon lives and the reason he was forced to leave his job, and to make clear the 1918 flu’s link to encephalitis lethargica was never established