Photographs by Jonno Rattman
Image above: Nearly a year after she was infected with the coronavirus, Caitlin Barber still uses a wheelchair outside.
This article was published online on March 8, 2021.
The quest at Mount Sinai began with a mystery. During the first wave of the coronavirus pandemic in New York City, Zijian Chen, an endocrinologist, had been appointed medical director of the hospital’s new Center for Post-COVID Care, dedicated both to research and to helping recovering patients “transition from hospital to home,” as Mount Sinai put it. One day last spring, he turned to an online survey of COVID‑19 patients who were more than a month past their initial infection but still experiencing symptoms. Because COVID‑19 was thought to be a two-week respiratory illness, Chen anticipated that he would find only a small number of people who were still sick. That’s not what he saw.
“I looked at the number of patients that were in the database and it was, I think, 1,800 patients,” he told me. “I freaked out a little bit. Oh my God, there’s so many patients telling us that they still have symptoms.” A realization dawned on him: America was not simply struggling to contain a once-in-a-century pandemic, caused by a virus far more dangerous than seasonal influenza. Many patients were, for unknown reasons, not recovering.
“We didn’t expect this from a virus,” he continued. “We expect that with viral infections as a whole, with few exceptions, you get better.” Many patients who spend significant time in an ICU—whether battling an infection or recovering from a stroke—do require further treatment even after they are released, because they suffer from something called post–intensive care syndrome, often characterized by weakness and cognitive problems. But that didn’t explain the group Chen was looking at. Startlingly, most had had mild cases of COVID‑19—they had neither been hospitalized nor developed pneumonia. Before contracting the virus, many had had no known health issues. Yet they were reporting significant ongoing symptoms—“shortness of breath, heart palpitations, chest pain, fatigue, and brain fog,” Chen told me.
Chen quickly convened a multidisciplinary group of clinicians. The team began triaging patients with ongoing symptoms, referring them to specialists and teasing apart the causes. There were patients of all ages and backgrounds, with a wide array of problems, from persistent loss of taste and smell to chest pain. Some patients had been seriously ill, and they typically had the lung scarring, or fibrosis, that comes with COVID pneumonia; they were referred to pulmonologists for follow-up care. Others had readily observable heart problems, including myocarditis, an inflammation of the heart muscle, and were referred to cardiologists. Still others had blood clots. The extent of the damage COVID‑19 had done to them was highly unusual for a respiratory virus—and deeply alarming. But, Chen told me, “those were actually the luckier patients, because we could target treatment toward that.”
The unlucky remainder—more than 90 percent of the patients the center has seen—was a puzzling group “where we couldn’t see what was wrong,” Chen said. These tended to be the patients who had originally had mild to moderate symptoms. They were overwhelmingly women, even though men are typically hit harder by acute COVID‑19. (Acute COVID‑19 refers to the distinct period of infection during which the immune system fights off the virus; the acute phase can range from mild to severe.) And they tended to be young, between the ages of 20 and 50—not an age group that, doctors had thought, suffered the worst effects of the disease. Most of the patients were white and relatively well-off, raising concern among clinicians that many people of color with ongoing symptoms were not getting the care they needed.
These patients’ tests usually showed nothing obviously the matter with them. “Everything was coming back negative,” says Dayna McCarthy, a rehabilitation-medicine physician and a lead clinician at the center. “So of course Western medicine wants to say, ‘You’re fine.’ ”
But the patients were self-evidently not fine. An international survey by Patient-Led Research for COVID‑19, one of various groups drawing attention to persisting problems, asked nearly 3,800 patients with ongoing illness to describe their symptoms. A significant number—85.9 percent—reported having relapses in the months after their initial infection, usually triggered by mental or physical exertion. (Not all patients in this group had confirmed cases of COVID‑19, given that tests were hard to come by last March and April.) Many patients were experiencing severe fatigue and brain fog. Other patients suffered from chest tightness and tachycardia—a condition in which the heart beats more than 100 times a minute—when they stood up or walked. Others had diarrhea and lost their appetite; some had terrible bone pain. Nearly a quarter said they were still unable to work; many had gone on disability or taken medical leave. Patient groups of COVID‑19 “long-haulers” were springing up on Facebook and elsewhere online, where people shared data and compared notes about what they began to call “long COVID.”
One such patient, Caitlin Barber—who wound up at the Mount Sinai Center for Post-COVID Care this past fall—caught the virus in late March of last year at the nursing home where she worked as a dietitian. Barber, who is 28, was newly married and living in upstate New York. She ran half-marathons competitively; after work every day she went to the gym for two hours. Then she came home, made dinner for her husband, relaxed, and went to bed. “Everybody knows, that’s what I do every day,” she told me, speaking in the present tense. She paused. “I had a great life, a perfect life.”
Read: Long-haulers are redefining COVID-19
Barber’s case of COVID‑19 wasn’t bad. “It was kind of like a cold for me; I got very lucky in that respect.” Two weeks later, she went back to work. “Within three days, my world just crashed,” she said. She had difficulty writing simple reports. In the middle of a routine feeding-tube procedure—“Dietitian 101,” she told me—she found herself, tube in hand, unsure what to do next. She called her supervisor to take over. After a few such failed attempts to work, she went on medical leave.
Nearly a year later, Barber is mostly bedbound: “My symptoms change all the time. I’m happy if I can take a shower.” She struggles to brush her teeth or prepare meals, because her heart races to 180 beats a minute. (A typical rate is 60 to 100.) Convulsions sent her to the emergency room in September. She is alone most of the day—her husband works long hours—and she has to plan carefully in order to use the bathroom and feed herself without collapsing. There are chairs placed strategically throughout her apartment for her to rest on. Her friends ask her what she does all day at home. “I feel like I am very busy,” she told me drily. It can take her a whole day to wash her bedding, because of the spikes in her heart rate.
Early on, many doctors, predictably, dismissed these cases as the result of anxiety or hypochondria. But at Mount Sinai, Chen and others tried to figure out what was happening. Their interest was not just academic. Beyond the terrifying impact on individual lives, the scope of the problem immediately alarmed them. “My goodness, the economic implications of this,” McCarthy told me. “You’re talking a huge number of 20-to-40-year-olds—our workforce—who now can’t work.”
Today, informal estimates suggest that 10 to 30 percent of those infected with the novel coronavirus have long-term symptoms. “What people need to know is the pandemic’s toll is likely much higher than we are imagining,” Craig Spencer, the director of global health in emergency medicine at New York–Presbyterian/Columbia University Irving Medical Center, told me. “It is an area that merits urgent attention. There will be people living with the impact of COVID long after the pandemic is over. This is not made up or in the minds of people who are sickly. This is real.”
And so, even as research scientists were developing the vaccines that will help bring an end to the acute phase of the pandemic later this year, the doctors at Mount Sinai and other academic medical centers began working to understand, and treat, the destruction that it is leaving behind. The unusual speed and scale of the effort are born of urgency. In many ways, the pace of progress has been remarkable, and innovations of a surprisingly low-tech sort are yielding results. But we still face a crisis of as-yet-unknown proportions that may change our medical system, our ideas about infectious disease—and the future of millions of Americans.
Last April, the quest became the consuming focus of another group of Mount Sinai clinicians, known for its novel approaches to problems for which medicine doesn’t have easy answers. David Putrino is the director of rehabilitation innovation for the Mount Sinai Health System. Putrino spends his time on questions that many doctors don’t think about, including “measuring things that are hard to measure,” he told me. Before the pandemic, he was treating professional baseball and basketball players in his “high performance” clinic and doing TEDx Talks about the brain’s remarkable ability to heal itself. After the pandemic hit, with ICUs full and the hospital overtaxed, Putrino’s team built a platform to remotely monitor patients with suspected coronavirus infections who at other times might have been admitted to the hospital. This triage helped many sick patients stay out of the ER while Putrino’s team watched their oxygen levels.
“And then my team started seeing these cases that weren’t getting better,” he told me. “My physical therapists were saying, ‘These symptoms are really different from those of acute COVID. We don’t know what to do with them.’ ”
When Putrino looked at the data, he saw the same symptoms that Chen saw. To Putrino, they looked like those of patients who suffer from a poorly understood and often misdiagnosed condition, one that he happens to know a lot about because his wife lives with it: dysautonomia, or impairment of the usual functioning of the autonomic nervous system, which controls blood pressure, temperature regulation, and digestion. Dysautonomia is itself an umbrella term for a host of different conditions, many of whose causes have yet to be fully pinned down. In common manifestations of it, a patient’s autonomic nervous system has trouble regulating the heart’s response to exertion, changes in posture, or variations in temperature, sending the body into an inappropriate fight-or-flight response. Some patients’ systems have trouble adjusting blood pressure or constricting blood vessels to send blood to the brain. Blood can pool in the legs and peripheries of the body; the heart might compensate by increasing its rate, while the body releases surges of adrenaline in a fruitless attempt to correct the problem. As a result, patients can experience some blend of fatigue, headaches, digestive problems, heart palpitations, difficulty breathing, and cognitive issues such as brain fog.
By chance, Putrino had been working on a project for dysautonomia patients with Amy Kontorovich, a genetic cardiologist at Mount Sinai who studies the condition and has treated hundreds of patients with it. (After they met, Kontorovich ended up diagnosing and treating Putrino’s wife, who has Ehlers-Danlos syndrome, a group of genetic disorders that affect the body’s connective tissues; it is commonly associated with dysautonomia.) And so, as the team showed him the cases, Putrino told me, he felt a leap of recognition. “I looked at the symptoms and was like, ‘Oh my God.’ And I called Amy and said, ‘Help.’ ”
Kontorovich was prepared for the call. A key clue had come her way : Two weeks earlier, she had received an email from a doctor she knew named Jessica Cohen, a 38-year-old who worked at a New York–area hospital. Cohen had tested positive for COVID‑19 on March 8—at the start of the first wave in New York—a few days after her husband returned from a trip to Scotland feeling logy. The couple have two young children. “I told him to ‘get over it,’ ” she says. “In retrospect, that may not have been the right thing to say.”
At first her illness was relatively mild, like her husband’s. Tracking her oxygen levels and heart rate with her smartwatch, she felt she had gotten lucky. But on the eighth day—March 16—she went to the bathroom, and her heart began to race, beating more than 140 times per minute. Worried she had a blood clot, she texted a colleague, who told her to go to the ER. No one yet had any idea what COVID‑19 did to the heart.
Meghan O’Rourke: Americans have to accept uncertainty about the coronavirus
Cohen went to the Mount Sinai ER, where she was admitted so that doctors could observe her racing heart. But the tests that help identify risk of clots and heart attacks came back normal. The doctors couldn’t figure out what was wrong. They told Cohen they thought she just needed “some more time”; she might be weakened from a week in bed. Thinking that she needed to start pushing herself, she went home.
That week, she forced herself to walk up the stairs in her house, only to collapse at the landing. She started having diarrhea and bouts of intense fatigue and severe headaches. One day she walked four blocks with her daughter to the store, where her heart began racing so fast that she had to sit down on the sidewalk until her husband came to pick them up.
Cohen began posting in a doctors’ group on Facebook, eager to find out whether any of her colleagues had patients whose symptoms resembled hers. On the afternoon of March 26, she sat up in bed, and her heart rate skyrocketed. “I had an epiphany,” she told me. “I thought, Wait a second. Oh my God. This is like POTS”—postural orthostatic tachycardia syndrome, one of the subtypes of dysautonomia. She began sleuthing—and turned up a paper that suggested a connection between POTS and an inflammatory immune response common in cases of COVID‑19. Excited, she posted a question: Had anyone’s patients experienced dysautonomia after the virus? None had. But one friend wrote back: “You need to talk to Amy.”
Cohen shared her medical chart with Kontorovich. “She was the first post-COVID patient I had seen. At that point, she clearly fit a picture of dysautonomia,” Kontorovich told me. After they spoke, she had a sinking feeling: “If this is something that happens to a lot of people, we’re in trouble,” she remembers thinking, “because most doctors don’t recognize dysautonomia as a real entity.”
When Putrino called Kontorovich, in May, the two began sharing their parallel experiences. Given the mounting evidence on his platform of the extent of ongoing illness, Putrino pulled together a group that started having weekly Zoom meetings. As a clinician who’d emigrated from Australia, Putrino still hadn’t gotten used to the American health-care system’s signature mode—“everything is very hyperspecialized, and professionals don’t speak to one another.” The group he assembled was, like Chen’s, notably multidisciplinary. In addition to Putrino and Kontorovich, it included a physical therapist, a sports-medicine physician, a respiratory specialist, and a nutritionist—all of whom had been trained to work holistically to treat conditions for which clear-cut medical protocols don’t exist.
Putrino and Chen connected, too. Because it conducts research, the Center for Post-COVID Care accepts only patients with positive COVID‑19 tests, but in the early days of the pandemic, thousands of patients had never been able to get a test at all. Chen started sending some of those patients to Putrino’s team.
Clues, initially, were sparse. “What we’re seeing is an entirely distinct syndrome,” Putrino told me, one that tends to be “way more debilitating and severe” than others like it, but similarly mysterious. No one knew exactly why the virus was throwing the autonomic nervous system out of whack—or causing all the other symptoms patients were reporting—but many suspected that the effect was likely to be “immune-incited,” as Dayna McCarthy put it. Based on preliminary evidence, some theories speculate that long COVID is a result of a powerful immune reaction unleashed by the virus, leaving widespread damage in the body; others posit that the immune response to the virus triggers autoimmune disease; and still other theories suggest that the virus itself causes hard-to-observe damage in the nervous system and other parts of the body. Or perhaps a combination of these factors is at play in different patients.
But drawing on Jessica Cohen’s case, and the reports of patients on the platform, Putrino and Kontorovich quickly developed a broad hypothesis: In a group of patients, they theorized, either the virus or the immune system’s reaction to it had caused dramatic dysregulation of the autonomic nervous system. In the absence of clear data, Putrino told me, they decided to study how patients responded to treatment. Patients with cardiac or pulmonary problems typically react well to rehab that pushes them physically (“if you can take a little more, we’ll push you a little more,” as Putrino put it). But that push-through-it model can dramatically exacerbate dysautonomia patients’ symptoms, causing exhaustion and a racing heart. So standard rehab usually doesn’t work.
Read: The core lesson of the COVID-19 heart debate
Experimentation with POTS over the past decade has yielded a paradoxical axiom that the group used as a guiding principle: Very gentle rehab is important, if you can tolerate it. The regimen involves doing short bursts of cardiac exertion while lying down or seated (so as not to tax the nervous and cardiovascular systems), wearing compression garments (to reduce blood pooling), hydrating, and taking salt (to increase blood volume). Studies, including an ongoing one conducted by Kontorovich’s lab, have found that in dysautonomia patients, the heart is smaller, and has less blood-volume capacity, than would be expected. No one knows if these patients’ hearts have actually shrunk in response to illness or other stresses—the phenomenon turns up in endurance athletes who suddenly stop training—or if people with smaller hearts are just more vulnerable to dysautonomia and related conditions. But studies have shown that targeted rehab can safely help the heart increase in size, improving symptoms. Putrino and Kontorovich theorized that the same might be true for the patients they were seeing.
Their hypothesis was borne out in a preliminary study, which found that a majority of their patients’ hearts were smaller than expected. And in rehab, people responded “more like we expected them to respond if they had autonomic issues than if they had cardiac or lung injuries,” Putrino said.
The patients’ symptoms were too varied to be lumped under an established label; in some ways the condition resembled dysautonomia, and POTS in particular—but it was not textbook. (Some clinicians began calling it post-COVID POTS.) In other ways, it closely resembled myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), in which people also demonstrate exercise intolerance and profound fatigue, but it was likewise not textbook. Same for autoimmune disorders. A commonality stood out: These are all poorly understood conditions that, evidence suggests, can be triggered by the body’s response to infections, with clusters of system-roaming symptoms that get grouped under one name.
In conjunction with a group of physicians in the U.K., Putrino’s team came up with a name, “post-acute COVID syndrome,” to distinguish between this manifestation of long COVID and the ongoing symptoms caused by observable organ damage from the virus.
Putrino’s team partnered with immunologists and researchers at Mount Sinai, as well as the National Institutes of Health and Yale, to try to identify the biological markers of post-acute COVID syndrome, and to understand the role the immune system was playing—but that kind of research takes months, if not years, to complete. In the meantime, the Mount Sinai teams struggled to find treatment protocols that worked for everyone to whom the new label seemed to apply. Some of their patients were so sick that even gentle rehab worsened their symptoms (much as people with ME/CFS have long reported). In others, rehab worked, but only up to a point, or patients overexerted themselves and relapsed. In April, for instance, Kontorovich had given Cohen a set of guidelines that made her strong enough to go back to work at the height of the surge in New York. But after working a 12-hour shift at the hospital treating COVID‑19 patients, Cohen ended up back in the ER and then at home, in bed.
A MISSING PIECE of the puzzle, the Mount Sinai teams soon found, was right in front of them: breathing. Everyone knew, of course, about severely sick COVID‑19 patients on ventilators. What the researchers and doctors at Mount Sinai hadn’t realized was that even mild cases might be affecting respiration after the acute phase of the disease. Evidence began to accrue that long-COVID patients were breathing shallowly through their mouths and into their upper chest. By contrast, a proper breath happens in the nose and goes deep into the diaphragm; it stimulates the vagus nerve along the way, helping regulate heart rate and the nervous system. Many of us breathe through our mouths, slightly compromising our respiration, but in patients with post-acute COVID syndrome, lung inflammation or another trigger appeared to have profoundly affected the process. In these cases, patients’ breathing “is just completely off,” McCarthy told me.
Over the summer months, Chen’s and Putrino’s teams refined their treatment approaches, observing and analyzing all the while. They addressed patients’ disparate symptoms (such as new food sensitivities, or roaming pain) with dietary changes, stress-management techniques, and individually tailored rehab. In addition, they introduced a science-based breathwork program, designed by a new company called Stasis, to try to restore normal breathing patterns in the sickest patients. Jessica Cohen used it over the summer to help recover from her setback. For Caitlin Barber, breathwork came in the fall, more than half a year into her ordeal.
The Stasis program is deceptively simple and strikingly low-tech: It involves inhaling and exhaling through your nose in prescribed counts in the morning and at night. The protocol was developed by Josh Duntz, a Navy Special Operations veteran, and his co-founder, Dan Valdo. During a decade in the Navy—he left in December 2019—Duntz had become obsessed with physical and mental performance under stress. “It was quite literally the difference between life and death,” he told me. Trying breathwork himself after a workout partner introduced him to it, Duntz noticed immediate improvement in his endurance runs: He could run for longer with a lower heart rate, and without getting tired. He dug into the emerging science of breathing and became a convert.
By luck, Duntz knew Putrino; the two had been working together on a project prior to the pandemic. In the spring, he heard about the persistent breathing problems of COVID long-haulers. One night in April, he woke up with an idea and scribbled “breathwork” in his bedside notebook. “So I reached out to David to say, ‘I think this could work and here’s why.’ ” A piece had clicked into place for Duntz: Similar symptoms (fatigue, shortness of breath, racing heart) occur in people who have low carbon-dioxide levels in their blood—a condition known as hypocapnia, which can be triggered by hyperventilation, or shallow, rapid breathing through the mouth. Duntz wondered if perhaps these long-COVID patients, so many of whom suffered from dizziness and tachycardia, were also breathing shallowly, because of either lung inflammation even in mild cases or viral damage to the vagus nerve. The theory seemed plausible to Putrino: Oxygen is key to our health, but carbon dioxide plays an equally crucial role, by balancing the blood’s pH level. Mount Sinai was able to launch a breathwork pilot program swiftly because of “how desperate people were—the hospital was so overwhelmed,” Duntz said. The program also didn’t have to pass FDA clearance.
After a week, everyone in the pilot program reported improvement in symptoms like shortness of breath and fatigue. (No double-blind randomized controlled trial has yet been conducted, so it is not possible to know what percentage of the improvement was due to the placebo effect.) The patients’ responses were “game-changing,” Putrino told me.
The key was the realization that the diaphragm and the nervous system had to be coached back to normal function before further reconditioning could start. “You cannot rehabilitate someone when their symptoms are completely out of control,” Putrino said. Although patients still faced an unfolding array of unpredictable symptoms, breathwork helped get them to a “place where the healing can start.”
That was Barber’s experience. In early November, seven months after getting sick, she began doing the breathwork with her husband, inhaling through the nose for four counts and exhaling for six in the morning, and in the evening, inhaling for four, holding for four, and exhaling for four. (I tried these routines and found them surprisingly hard.) She immediately discovered that she could better calm herself during an episode when her heart began racing.
Dayna McCarthy at the Center for Post-COVID Care laid out the group’s theories about why the treatment is so helpful. Through breathwork, patients can consciously control their heart rate, she noted. In addition, modulating the nervous system’s fight-or-flight response may help regulate the immune system. (Studies have shown that elevated stress hormones can lead to chronic inflammation.) And proper breathing is crucial to circulation in the lymphatic system, often described as the body’s highway for immune cells, which plays a role in eliminating toxins and waste.
I talked with Barber a few weeks after she started the breathwork. She had noticed a dramatic decline in her heart rate. “It doesn’t help with my mobility,” she said. But “for some reason, my symptoms”—of breathlessness, dizziness, and brain fog—“have noticeably lessened.” She had her period the week we talked, usually a time when her symptoms intensified, but that month they hadn’t.
IF THERE IS any reason for hope in the growing epidemic of long COVID, it is that some academic medical centers are taking these patients seriously and tailoring treatment to them. Medicine’s history with hard-to-identify chronic illnesses, particularly those that mainly affect women, has not been a good one. For decades now, marginalized patients who have felt mysteriously unwell—with ME/CFS, with post-treatment Lyme disease syndrome, with Ehlers-Danlos syndrome, and more—have banded together into activist groups to try to legitimize their suffering. The same is happening online in the long-hauler groups, which are full of patients who have been met with disbelief by local physicians. But the Mount Sinai doctors (along with collaborative teams in various other academic centers) have responded promptly to the problem. Recently, the NIH and the World Health Organization recognized long COVID as a syndrome that warrants more research.
From the September 2019 issue: Meghan O’Rourke on why Lyme disease is so hard to understand
Why? Because of the sheer scope of the problem, to be sure. But also because when patient groups began calling attention to it, they were reaching out to clinicians who were primed to listen. After all, many of those who first reported the experience of relapses and persistent trouble are doctors, like Jessica Cohen. Another such doctor is Dayna McCarthy, who struggles with long-COVID symptoms. “These are doctors that we work alongside,” Chen told me. “And we know that these aren’t patients that are faking it. If my fellow doctor, whom I work with closely, is telling me that they can’t get through the day because they can’t think straight, I’m going to believe that.”
In these places—most notably, Mount Sinai, UC San Francisco’s post-COVID center, and Johns Hopkins—the people treating long-haulers were already champions of thinking in new ways about chronic illness. Amy Kontorovich, for instance, has been treating dysautonomia patients for almost a decade, and she’s become passionate about advocating for patients whose conditions are dismissed. “Most of my patients were young women between the ages of 20 and 45. And the story was often one of a long diagnostic journey,” Kontorovich told me. “Patients had been told symptoms were in their head or purely due to anxiety.” Her patients epitomize the kind whom the medical system frequently fails—by contesting the reality of their illness, sending them from specialist to specialist, loading them up with drugs without getting to the root cause.
From the November 2014 issue: Meghan O’Rourke on how doctors and patients communicate
Doing better by these patients has been challenging because 20th-century medicine was not really built to treat hard-to-measure systemic illnesses—especially those, like dysautonomia, ME/CFS, and autoimmune diseases, that can be worsened by stress. Instead, it was based on the rather incredible notion that all bodies respond roughly the same way to infection or injury, and the immune system is a well-organized defense mechanism that never attacks the body. This perspective is turning out to be oversimplified.
The framework dates back to the embrace of germ theory in the late 19th century. The idea that many illnesses are caused by an observable pathogen, which produces distinct and predictable symptoms, had a dramatic clarity to it. It pushed Western medicine away from an earlier holistic emphasis on the role an individual’s constitution played in illness. According to the new view, infection was determined by a specific and measurable entity. Focus had shifted from the soil to the seed, as it were.
This pivot increased survival rates from infectious diseases and gave us longer lives, on average. But it had one particularly negative consequence: Patients who reported inexplicable ongoing problems after an infection were largely ignored or dismissed by physicians if tests failed to turn up clear answers.
In recent years, though, medical pioneers have pushed past the “if we can’t measure it, it doesn’t exist” view, bringing the individual constitution—the soil—back into consideration, and articulating a more current idea: that the immune system’s response to a pathogen could be what does much of the damage to our bodies. This new paradigm holds that disease is a multipronged phenomenon—an interaction among pathogens (whether viruses or bacteria), the immune system, and “environment,” a term that can refer to one’s microbiome or one’s exposure to such things as toxic chemicals and trauma. (Both have been shown to affect the immune system.) At the vanguard of an emerging personalized medicine, the new view of postviral illness takes into account the variety of individual immune responses to infections, which, we now know, are influenced by the social and genetic determinants of health, among them the stresses of poverty and systemic racism.
This paradigm suggests that in fact—though Chen had expressed initial surprise to see a virus acting this way—a wide array of infections may routinely trigger long-term illness in certain patients. A 2018 study conducted by researchers at the Cincinnati Children’s Hospital showed that Epstein-Barr virus, which develops into mononucleosis, increases the risk of lupus in a genetically susceptible group of people. Researchers at Stanford are exploring immune pathways by which certain infections (for example, strep throat) can trigger pediatric acute-onset neuropsychiatric syndrome in some children.
COVID‑19 seems like a test case for this new model of thinking about infection as a trigger of immune dysfunction: One of the disease’s great mysteries is why some 30-year-olds die from it while others barely notice they have it, and still others initially have a mild acute case but end up unable to manage a flight of stairs. This pandemic has vividly dramatized the variability—and lingering complexity—of the human host’s response to a pathogen.
“This is something that has been going on forever,” said Craig Spencer, the director of emergency medicine at Columbia University Irving Medical Center. Spencer understands something about postviral conditions, because he contracted Ebola while working in Guinea and fell ill upon his return to New York City, where he then also struggled with its aftereffects.
“I wouldn’t be surprised if people are walking about with long Epstein-Barr virus, or long influenza. We all know someone who is low energy, who’s told to work harder. We have all heard about chronic-Lyme sufferers, and those with ME/CFS. But they get written off,” Spencer told me. The difference now is that it is happening “on such a huge scale—unlike anything we’ve seen before. It is harder for the medical community to write off.” Indeed, many researchers I spoke with believe that the race to understand long COVID will advance our understanding of chronic conditions that follow infection, transforming medicine in the process.
A GREAT DEAL REMAINS to be discovered about long COVID—about why more women than men seem to suffer from it (estrogen, genetics, and differences in the immune response are all being explored); about why some men experience erectile dysfunction; about how it affects taste and appetite, as well as mental health; about why some people respond to exercise-based rehab and others don’t. Proof of the virus’s destructive power keeps accumulating. One study found that a significant number of hospitalized COVID‑19 patients developed antibodies to their own tissue. Some research suggests that the virus persists in immunocompromised patients for many weeks. Evidence is also mounting that the virus infiltrates and damages not just the lungs and the heart, and possibly the vagus nerve, but also the brain, vocal cords, esophagus, and more. Doctors are experimentally treating long-COVID patients with a variety of pharmaceuticals, among them antihistamines, Pepcid AC, and an antiparasitic drug called ivermectin.
Medicine’s prompt attention to these patients has mattered, because successful management of post-acute COVID syndrome, whatever its specific catalyst, seems to be tied to timely treatment of it. As Putrino told me, “What we know from these sorts of conditions is the longer that you persist with the symptoms without having them managed, the longer it takes to eventually rehabilitate them.” In March, Jessica Cohen couldn’t walk up two flights of stairs. Today, she is back at work full-time, feeling lucky that much of her job is administrative and she can sit at a desk; even this much effort means managing flares that leave her depleted, her heart pounding when she tries to walk more than a short distance.
By contrast, by the time Caitlin Barber finally got into the Mount Sinai Center in mid-September—having learned about it from a patient Facebook group—“I had been dismissed and turned down and completely gaslighted by doctors for months,” she recalled. During that time, she got sicker and sicker. At the center, where Barber saw an intake doctor and was given a full cardiac evaluation, the doctors told her that her condition would not have become so severe if it hadn’t gone untreated for so long. They also told her that they now understood, five months in, that her symptoms resembled those of thousands of others, which few physicians had realized back in April. They believed her, and they could help, though they didn’t yet know what the path toward recovery might look like.
When I first spoke with her, in late October, Barber explained that she believed she was unlikely to make a full recovery, though she hoped for better quality of life.
Four weeks later, in late November, when we talked for a third time, the breathwork had led to some dramatic improvements, ameliorating the most debilitating of her symptoms: She could sit up without feeling dizzy. She had been cleared for physical therapy, which consisted of gentle strengthening of key muscle groups. The first rounds—done virtually with a therapist over videoconference—would take place with her lying down, so as not to stress her heart or nervous system.
In December, she and her husband went for a series of follow-up appointments at the center, one of them with her cardiologist, Ruwanthi Titano. Her husband FaceTimed me so I could watch. “How are you doing?” Titano asked. Perched on the exam table, Barber explained that she was taking the prescribed salt and doing the PT diligently. “I have made a little progress,” she said, with evident enthusiasm. Three months had passed since her first Mount Sinai visit; nearly eight months had passed since she was first infected.
“I don’t need the wheelchair in the house. I can shower and I can care for myself when he’s at work,” she said, turning toward her husband.
“She is able to go up and down the stairs now very slowly,” he broke in.
“That’s huge!” Titano exclaimed.
The excitement in the room was palpable even through the pixels of my screen. The treatment was working—if slowly and incrementally. Titano discussed the results of Barber’s latest tests; structurally, her heart looked fine. It was the autonomic issues that she had to keep working on. Barber explained that even a minor stressor like sitting in traffic while cars honked at her husband could still make her body shake with tremors.
“That goes with the POTS. You have all this circulating adrenaline,” Titano reassured her. “As we go on, we expect this to get better and better.”
They discussed plateaus, medications, and sticking to the exercises and her new diet over the holidays. Throughout, Titano listened closely as Barber discussed her ups and downs, supportively reiterating the kind of stress and lifestyle management required.
At the end, Barber asked Titano if she could actually expect to get better. Just six weeks earlier, I had had the sense that she was trying to close the door on such a prospect in order to adjust to her new life. But it is human to hope, and she had made so much progress.
Titano replied carefully: “On the spectrum of symptoms, you were on the more severe end when we started. But you’re definitely improving, and I can’t see a reason why you wouldn’t.” She paused. “But running might not come anytime soon!”
“I’m okay with that,” Barber said. “What we have going is working, so I’m okay with that.”
Barber, who has an athlete’s determined temperament, was putting a positive spin on the situation. “I am making progress. But the progress is not that I can walk two miles instead of one,” she later clarified to me. “It’s that I can walk for 20 seconds across a room.”
THE WAY Jessica Cohen and Caitlin Barber are being treated at Mount Sinai is a model for the care of patients with post-acute COVID syndrome. But Barber’s coordinated day of appointments was a far cry from the bare-bones 10-minute appointments that many of us are used to having with specialists who don’t speak with one another. In many places in the country, high-level medical care is hard to come by; underserved communities—whether their members are primarily rural, low-income, or people of color—have historically been less able to access such care. (Comprehensive statistics on long COVID’s impact on different ethnic and socioeconomic groups have yet to be gathered.) All of this raises the question of how—or if—we will have the resources to treat everyone in need. Hospitals make money by getting more patients in the door and out again. The care that long COVID demands may not be high-tech, but it is time-consuming and attention-intensive; clinicians need to tailor care to patients in ways that “our health-care system is not set up for,” as Dayna McCarthy put it. (This is one of the reasons that Mount Sinai’s waitlist has ballooned.) Medicine is used to the quick fix. This kind of syndrome, which can’t be treated with a pill and stubbornly resists straightforward rehab, “is not one that doctors like treating,” I heard from another doctor. As Putrino told me, many of Mount Sinai’s post-acute COVID patients are “on a road to recovery. But I would not say a single one of our patients feels like they did before they got sick.”
Researchers said that the CDC and the NIH need to take the lead on funding research into long COVID and educating doctors about its severity. But education and reform aren’t easy, even if the pandemic has delivered an unprecedented jolt to a generation of doctors. Cohen told me that in the past she had treated patients with POTS and found herself wondering, “What am I supposed to do for you? You’ve had this your whole life.” She had been taught very little about dysautonomia in school. Now she told me it was clear to her that ignorance “shouldn’t have been an acceptable answer.”
Back at Mount Sinai, the push for answers continued. Preliminary observations were yielding more data to support the theories about the role that breathing issues and autonomic dysfunction played for some patients. When Putrino’s team looked at patients’ carbon-dioxide levels, it found that all the patients had low CO2 levels when they first came to be treated. After doing the breathwork exercises, patients’ symptoms abated; the team plans to measure whether their CO2 levels rose. Seeing clinical reasoning pay off was reassuring.
The clock, though, is ticking for patients whose illness continues to defy tidy categorization and treatment. The hurdles are profound. “A lot of clinicians want the algorithm,” Putrino said. “There is no algorithm. There is listening to your patient, identifying symptoms, finding a way to measure the severity of the symptoms, applying interventions to them, and then seeing if those symptoms resolve. That is the way that medicine should be.” In the meantime, the human toll expands, and the long haul gets longer.
This article appears in the April 2021 print edition with the headline “Unlocking the Mysteries of Long COVID.”
