The nagging symptoms long-haulers experience reveal a frustrating blind spot in medicine.
Dr. Craig Spencer, an emergency room doctor in New York City, was no stranger to dangerous viruses when a brush with one landed him in Bellevue Hospital for 19 days. But it was only after he was discharged, and declared virus-free, that the really bizarre symptoms set in.
Back at home, he noticed he couldn’t taste anything for several days. For months, he was tired all the time and his joints felt heavy and painful. When he woke up in the morning, his back was “stiff like a bamboo rod.” His weight dropped, and clumps of hair fell out. Though the physical effects eventually faded, cognitive complications persist to this day — what he describes as “a subtle but noticeable difference in concentration and ability to form new memories.”
If Spencer’s constellation of ongoing symptoms — fatigue, muscle and joint pain, memory issues — sounds familiar, it’s because it has become a frightening feature of some coronavirus infections, an epidemic of long-term illness within the pandemic. For the Covid-19 “long-haulers,” symptoms can persist for weeks or even months, long after being discharged from the hospital or testing positive for the virus, if they even saw a doctor or got diagnosed at all.
But Spencer never had Covid-19. His persistent aches, pains, and memory problems arose after contracting Ebola in late 2014, when he was working with Doctors Without Borders in Guéckédou, Guinea, the epicenter of the West Africa Ebola epidemic. The experience has led him to join the growing chorus of health professionals, patient advocates, and researchers who argue we need to reframe how we think about coronavirus long-haulers.
The dominant narrative about long Covid has been that it’s a uniquely perplexing feature of Covid-19. Reports of “Covid brain fog” or “Covid dementia,” for example, suggest a disturbing and extraordinary ability of the coronavirus to destroy the lives of survivors. Even a year later, some patients are still struggling to return to work or have their illness recognized, let alone access disability benefits.
While there’s no doubt long Covid is a real condition worthy of diagnosis and treatment, “this isn’t unique to Covid,” Akiko Iwasaki, an immunologist at the Yale School of Medicine, said. Rather, Covid-19 appears to be one of many infections, from Ebola to strep throat, that can give rise to stubbornly persistent symptoms in an unlucky subset of patients. “If Covid didn’t cause chronic symptoms to occur in some people,” microbiologist Amy Proal told Vox, “it would be the only virus that didn’t do that.”
Even with growing awareness about long Covid, patients with chronic “medically unexplained” symptoms — that don’t correspond to problematic blood tests or imaging — are still too often minimized and dismissed by health professionals. It’s a frustrating blind spot in health care, but one that can’t be as easily ignored with so many new patients entering this category, said Megan Hosey, assistant professor at the Johns Hopkins Department of Physical Medicine and Rehabilitation.
“It has always been [and] is the case that patients who get sick experience high levels of symptoms like those described by long-Covid patients,” she said. “We have just done a terrible job of acknowledging [and] treating them.”
Doctors have noticed long-term illnesses after an infection since at least 1889
For a while after the coronavirus began spreading in China in late 2019, many doctors viewed it as a “viral pneumonia” that mainly threatened the lives of elderly people. The virus seemed to cause only a short list of symptoms, including fever, dry cough, and difficulty breathing. According to a February 2020 World Health Organization report, mild cases recovered within two weeks, while it took up to six weeks for those with severe or life-threatening illness to get better.
By March, patients on social media started drawing attention to much longer-term symptoms, which sometimes appeared after mild cases in young, otherwise healthy people. In April, Fiona Lowenstein, a 27-year-old Covid-19 advocate and writer, penned one of the first widely circulated long-Covid accounts, sharing her experience of symptoms like gastrointestinal issues and loss of smell. She presciently warned that a “wave of chronically ill and slow-healing survivors is an inevitability we can and must prepare ourselves for.”
Today, doctors are more aware that Covid-19 can affect every system in the body. There’s still no official name for long Covid — which also goes by chronic Covid syndrome, post-Covid-19 syndrome, and post-acute Covid-19. There’s also no official definition. Researchers generally use time to make a diagnosis: patients who experience at least three or four weeks of symptoms that develop during or following a confirmed or suspected coronavirus infection.
The true spectrum of long-Covid symptoms is, however, coming into focus. A recent preprint (non-peer-reviewed) paper, led by Hannah Davis — a Covid long-hauler and administrator of Lowenstein’s long-Covid patient support group Body Politic — surveyed 3,762 patients from 56 countries who were sick for at least four weeks. They documented an array of 205 symptoms involving 10 organ systems, from tremors, tingling and skin burning, to sleep disturbances, nausea, chest tightness, and hearing loss.
Most common were fatigue, cognitive dysfunction, and post-exertional malaise, defined as a “worsening or relapse of symptoms after physical or mental activity” during Covid-19 recovery. More than 90 percent of those in the study hadn’t been admitted to a hospital. Most (nearly 80 percent) were women. One in five reported severe symptoms persisting after six months.
The nagging symptoms, though certainly unnerving, aren’t unprecedented. Chronic symptoms, especially fatigue, have lingered after the typical recovery periods for viruses as varied as West Nile, Dengue, Zika, seasonal flu, and H1N1 as well as the new coronavirus’s cousins MERS and SARS-1. Run-of-the-mill strep throat can develop into rheumatic fever, which causes similarly painful and stubborn after-effects as long Covid. I lost one summer in college to mononucleosis, caused by the Epstein-Barr virus; for weeks, I had no appetite and could hardly muster the energy to get out of bed.
The phenomenon, sometimes called “post-viral syndrome,” has been documented for more than a century, as far back as the 1918 Spanish flu, when there were Spanish flu long-haulers — scores of people who survived the deadly virus but had long-term symptoms, including depression, sleeplessness, “loss of muscular energy,” and “nervous complications.”
Even “Covid dementia” isn’t really new: According to a recent historical review, early reports of the “common symptom of altered cognition” surfaced during the Russian flu pandemics of 1889 and 1892.
“I can’t find a single thing that the SARS-CoV-2 virus can do, that other viruses cannot,” Proal said. “It’s well understood and it’s been understood for decades that every major pathogen capable of infecting people has a syndrome associated with it in which a certain number of patients who get that pathogen … will develop chronic symptoms that never go away.”
Craig Spencer, the Ebola long-hauler, only began to contemplate this pattern after the initial pandemic emergency in his New York City hospital abated late last spring. No longer filled to capacity, a broader spectrum of patients — not just the deathly ill — started seeking care.
The “tide reced[ed] and you’re there to observe the damage,” he told me recently. “I saw a lot of people saying they’d been to a bunch of different doctors. They know they had Covid. [The doctors told them] they didn’t know how to help them or that it was all in their head and that they probably needed to see a psychiatrist.”
In September, Spencer wrote about the parallels between his experience with long-haul Ebola and what he was hearing from these Covid-19 patients. “That’s when I started recognizing that this toll was going to be a lot bigger than anyone had recognized,” Spencer said.
The wave of patients is still growing. Of the more than 118 million coronavirus cases around the world, at least 10 percent of those affected may have long-term symptoms. That means that in the US alone, there could already be 3 million long-haulers — nearly six times the official US Covid-19 death toll. With numbers this large, Spencer said, maybe those with other little-understood chronic conditions, who have been “cast aside or undermined, disbelieved by the medical community” for decades, will finally get the recognition they’ve been waiting for.
It’s not just viruses that can trigger long-haul illnesses
Myalgic encephalomyelitis/chronic fatigue syndrome is one of those persistently under-recognized, underfunded, chronic conditions. ME/CFS, as it’s known, afflicts up to 2.5 million Americans every year, mostly women, with persistent symptoms ranging from fatigue and dizziness to sore throat and muscle pain. Recently, ME/CFS patients and their doctors have been pointing to the overlap with long Covid, conditions that US health official Anthony Fauci has called “very strikingly similar.”
Diagnoses of ME/CFS are made on the basis of symptoms, and some long-Covid patients meet the diagnostic criteria for the syndrome. Post-exertional malaise, for example, is considered “the cardinal symptom” of ME/CFS, Jaime Seltzer, director of scientific and medical outreach at the ME/CFS advocacy group ME Action. It’s also something nearly 75 percent of long-Covid patients reported in the recent long-hauler preprint. In another recent paper, researchers called on physicians to familiarize themselves with ME/CFS as the pandemic could “at least double” the number of cases.
There’s debate about what causes ME/CFS. Some view it as a genetic disease; others believe it’s triggered by viruses. A 2006 study followed 253 patients who’d been diagnosed with Epstein-Barr virus (the cause of mono), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) for a year and found 12 percent were diagnosed with ME/CFS within six months.
Post-viral syndrome and ME/CFS also parallel other contested and little-understood chronic disorders, including chronic Lyme disease, which is thought to occur after infection with the tick-borne Borrelia bacterium. Johns Hopkins’s Megan Hosey opened the long-haul umbrella even wider, beyond viruses and bacteria, to illnesses like cancer, multiple sclerosis, Type 1 and 2 diabetes, and lupus.
“A proportion — usually around 30 percent — of survivors of any medical condition report high rates of fatigue, sleep disturbance, brain fog, pain, depression, and anxiety that interfere with their ability to live fully,” she said. Diseases like cancer and Covid-19 may have different causes, but they share something in common when symptoms persist: If doctors can’t find a biological explanation for what’s troubling their patients, patients have trouble being believed. “I think a lot of patients [feel], ‘This physician doesn’t get it,’ or, ‘This physician thinks it’s all in my head.’”
The idea that long-Covid symptoms have a psychological basis came up at a recent research meeting Proal attended. A colleague noted the fact that more women than men present with the condition. “[What] was really thrown out as one of the top scenarios: Women are very anxious,” Proal recalls. Researchers who’ve investigated psychiatric and psychosomatic triggers for chronic conditions like ME/CFS, for example, have found no consistent link. “So maybe that really would not be the first direction you would go in with long Covid. … These are biological diseases driven by biological causes and they really don’t seem to be diseases of the psyche.”
Other chronic illnesses make long Covid less mysterious
Seeing long Covid in this context makes the condition less mysterious. Other long-haul illnesses also shed light on what might be sickening coronavirus long-haulers.
We’ve learned from other viral infections that, in some cases, pathogens do not fully clear the body. “It’s out of the blood but gets into tissue in a low level — the gut, even maybe the brain in some people who are really sick — and you have a reservoir of the virus that remains,” Proal explained. “And that drives a lot of inflammation and symptoms.”
These reservoirs have been documented following infections with many other pathogens. During the 2014-2016 Ebola epidemic, studies emerged showing the Ebola virus could linger in the eye and semen. There were similar findings during the 2015-2016 Zika epidemic when health officials warned about the possibility that Zika could be sexually transmitted. (Viral reservoirs are why the moniker “post-viral” can be problematic, Proal added.)
A related explanation for what might be happening with long-Covid patients is what Yale’s Iwasaki calls “viral ghosts.” While the intact virus may have left the body, “there may be RNA and protein from the virus that’s lingering and continuing to stimulate the immune system,” Iwasaki said. “It’s almost like having a chronic viral infection — it keeps stimulating the immune system because the virus or viral components are still there, and the body doesn’t know how to shut it off.”
In autopsies of people with chronic fatigue syndrome, researchers have also found enteroviruses and their RNA in patients’ brains, including, in one case, in the brain stem region. The brain stem controls sleep cycles, autonomic function (the largely unconscious system driving bodily functions, such as digestion, blood pressure, and heart rate), and the flu-like symptoms we develop in response to inflammation and injury. “If that area of the brain signaling becomes dysregulated [by viruses or viral ghosts],” Proal said, “[that] can result in sets of symptoms that meet a diagnostic criteria for [chronic fatigue syndrome], or even for long Covid.”
Other pathogens already lurking in the body prior to a coronavirus infection might also exacerbate symptoms. For example, viruses in the herpes family — such as Epstein-Barr (the cause of mono) or varicella zoster (the cause of chickenpox and shingles) — stay dormant in the body forever. Under normal conditions, the immune system can keep them in check. But when we’re under stress or fighting off another disease, the herpes viruses may activate again. In this case, part of what’s causing the long-Covid symptoms could be the body’s immune response to non-coronavirus pathogens that have reawakened.
Another key hypothesis: Long-Covid patients have developed an autoimmune disorder. The virus interrupts normal immune function, causing it to misfire, so that the molecules that normally target foreign invaders — like viruses — turn on the body itself. These “rogue antibodies,” known as autoantibodies, “attack either elements of the body’s immune defences or specific proteins in organs such as the heart,” according to Nature. The assault is thought to be distinct from cytokine storm, an acute immune system disorder that appeared as a potential threat early on in the pandemic.
For coronavirus patients who had to be admitted to intensive care units, there’s yet another explanation: Long before the pandemic, the intensive care community coined a term for the persistent symptoms people frequently experience following stays in an ICU for any reason, from cancer to tuberculosis. These symptoms included muscle weakness, brain fog, sleep disturbances, and depression.
The term “post-intensive care syndrome” was “created to raise awareness and education, because so many of our ICU survivors were going to their primary care doctor saying they were fatigued,” said Dale Needham, who has been treating Covid-19 patients in the ICU at Johns Hopkins. “They had trouble remembering, and they were weak. Their primary care doctor would do some lab tests and say, ‘Oh, there’s nothing wrong with you.’ The patient might walk away and feel like the doctor was saying, ‘It’s all in your head. You’re making it up.’”
The Covid-19-inspired medical revolution
Needham was getting at something I heard again and again from the many patients, researchers, and health professionals I spoke to for this story: If long Covid changes anything, it has to be this knee-jerk reaction in medicine to discount and give up on patients with symptoms that have no identifiable biological basis. The experience is so pervasive that researchers at the Mayo Clinic in Minnesota gave it a name: “undercared-for chronic suffering.”
There are certainly many systemic explanations for under care — from a lack of access to health care or medical insurance to the mere minutes that now characterize the length of the average medical appointment. But it’s also true that something more basic is exacerbating the problem. Simply put, medicine hasn’t cracked how to deal with patients who have chronic syndromes, like ME/CFS or long Covid, that don’t have one-size-fits-all treatment regimens.
People “want disease to kill you, or they want you to return to miraculous good health,” said Seltzer. “When you stay sick, compassion can fade. And that is not just friends and family. That is your clinicians as well; they want somebody fixable.”
Instead, long-haulers of any chronic condition can exist in a space between sickness and health for years, sometimes without a diagnosis. Their unexplainable symptoms can elicit skepticism in health professionals, Proal said, who are trained to consider patient feedback the “lowest form of evidence on [the evidence hierarchy], even under research on mice.”
With wartime levels of long-Covid patients now flooding health systems around the world, “it’s time for medicine to be rooted in just believing the patient,” Proal added. And not only believing patients, but also acknowledging and having compassion for the uncertainty they’re facing, Hosey said. Even without understanding the cause of someone’s suffering, “We can immediately start talking about treatment of symptoms and returning to life that’s full and meaningful because I think that that’s really what patients are asking for in the long run.”
This means doctors partnering with experts in other disciplines, such as rehabilitation psychologists or physical therapists, to tackle the unique problems a patient is experiencing.
It also means tailoring treatment. “It would be silly to assume that every patient that gets [long Covid] label has the exact same thing going on,” Proal said. For example, some long-Covid patients may have an ongoing infection while others have lung inflammation. The first group might benefit from “pacing,” a concept borrowed from the ME/CFS community that advises patients to listen to their bodies and avoid over-exerting themselves. The second group might benefit from regular exercise.
For now, many long-haulers report being gaslit and disregarded by medical professionals, especially if they don’t have a positive PCR test confirming the diagnosis. Of the dozens of medical appointments one Covid-19 long-hauler, Hannah Davis, had for her persistent symptoms — which include memory loss, muscle and joint pain, and headaches a year after her initial disease — one of her best experiences involved a doctor who simply said, “I don’t know.”
“The doctor [told me], ‘We are seeing hundreds of people like you with neurological symptoms. Unfortunately, we don’t know how to treat this yet. We don’t even understand what’s going on yet. But just know you’re not alone,’” she recounted. “And that’s the kind of conversation that needs to be happening. Because we can wait, but we can’t have the doctor’s anxiety being projected onto us as patients.”
Author: Julia Belluz