The COVID-19 Long Haulers
Nearly 1 in 3 coronavirus survivors have strange, often changing symptoms without known causes or cures. Here’s what they and their doctors are doing about it.
By Margaret Nicklas, Fri., March 26, 2021
For many of the unlucky people who have contracted COVID-19, the virus has led to numerous health problems that have persisted after recovery from their initial illness. These individuals have come to be known as "long haulers," experiencing what's sometimes described as "post-COVID-19 syndrome," or "long COVID."
The lack of an official term for this phenomenon is one of many aspects of COVID-19 that experts have yet to resolve. How long will symptoms last? What causes them? Why do some people experience long COVID while others don't? Why do symptoms vary so much? And perhaps most importantly, what can be done to treat or alleviate these effects? At this point, there are more questions than answers, but there is an increasing recognition that the condition is real and serious and that it's crucial that more answers be found.
"The diagnosis has proved extremely frustrating for care providers," said Dr. Nicholas Yagoda, associate chief medical officer for CommUnityCare in Austin, but it's been even more frustrating for the patients themselves, living through prolonged disability without any cure. Yagoda told the Chronicle earlier this year about caring for multiple patients who've recovered from COVID but who still struggle with persistent symptoms: shortness of breath, chronic fatigue, and loss of taste or smell. Some patients report "brain fog" and difficulty with memory and concentration, he said.
As time has passed since the emergence of COVID-19, it has become more evident that some survivors continue to experience persistent symptoms. Those early long haulers encountered "stigma or even gaslighting around the condition itself," Yagoda said. He thinks long COVID is now more widely understood to be real, but that coming to that diagnosis remains challenging. "And then it begs the question of once you have a diagnosis, how do you manage it?" he said.
The novel coronavirus known as SARS-CoV-2 that causes COVID-19 was first identified in Wuhan, in Central China, in late 2019; before it began infecting humans, the virus is believed to have lived among bats, but it didn't make them sick. As each immune system confronts the virus, we slowly gain knowledge of what SARS-CoV-2 does when humans are infected.
While science and medicine learn more every day, there's still enormous uncertainty about how exposure to the virus will affect people over time. The need to reduce that uncertainty is great. Long COVID appears to hit at least 30% of those infected with the virus, experts say, and maybe substantially more; that's tens of millions of people who may live with long-term if not lifelong effects in the U.S. alone. "If we even have a small percentage of individuals with persistent debilitating symptoms, we're going to have a wave of chronically disabled individuals in the coming years," Yagoda told us. "And that is frightening."
Many People, Few Answers
Because the numbers infected with COVID are so "shockingly large," as Yagoda says, even if the percentage with persistent symptoms proves to be less than 30%, long COVID would still become one of the more common chronic diseases in America, on par with Alzheimer's or chronic kidney disease. As of March 24, the Johns Hopkins Coronavirus Resource Center reported more than 124 million COVID-19 cases worldwide since the beginning of the pandemic last year, with 29.9 million of those here in the United States.
One local expert, Dr. Esther Melamed, is working to solve some pieces of this puzzle. An assistant professor of neurology at UT Dell Medical School, Melamed is collaborating with UT faculty members Lauren Ehrlich, Todd A. Triplett, and Jeanne Kowalski, along with other researchers, students, and clinicians in Austin, to understand how immune responses differ in patients who have mild or severe cases of COVID-19. Both can go on to experience long COVID. "It's not just the people who were in the ICU who are having persistent symptoms," she told us. "It's people who actually had very mild or asymptomatic [cases of the] disease who can go on to develop health complications that are not going away or take a long time to go away."
Many of these lingering problems are neurological – symptoms such as chronic fatigue, headaches, pain, loss of sensation, and persistent memory problems, Melamed said. Some post-COVID patients develop serious autoimmune conditions like transverse myelitis, Guillain-Barre syndrome, and multiple sclerosis, which can result in muscle weakness and paralysis. "Our research is also addressing how other factors like age, gender and ethnicity and prior autoimmune diseases interplay with immune responses to impact long-term health outcomes in patients who have been affected with COVID," with the goal of finding specific treatments and improving clinical care of patients, she said. The team hopes to have scientific updates from its studies this summer.
One specific condition developed by some long haulers is postural orthostatic tachycardia syndrome, or POTS. Dr. Tae Chung, an assistant professor of physical medicine and rehabilitation at Johns Hopkins and an expert on POTS, told us he was receiving many more referrals to his POTS clinic due to COVID-19. The condition, which can cause fatigue, brain fog, dizziness, general discomfort, and a rapid or unpredictable heart rate, is believed to be the result of dysfunction in the autonomic nervous system, which manages things we don't consciously control like sweating or blood flow to active muscles.
With POTS, a person's blood does not move to where it is needed – to the limbs, or to the brain – as well or quickly as it should. As a result, people with the syndrome may feel faint when they change positions, or "foggy" when they hold a position for a long time. It's not clear how or even if COVID-19 leads directly to this syndrome, which was already not well understood before COVID, Chung said. But he believes POTS could explain the suffering of some long haulers where heart disease or lung impairments that can cause similar symptoms have been ruled out.
Chung says patients with unexplained symptoms more than three to six months after a COVID infection – even an asymptomatic one – should see a doctor; if they have POTS, there are therapies that can help. In the past, POTS symptoms have often been dismissed, sometimes as anxiety or another psychological issue, because standard diagnostic test results were normal. Though the "T" in POTS stands for "tachycardia," many people with the syndrome don't report and aren't diagnosed with heart trouble, Chung said; they just feel very fatigued and generally uncomfortable. Doctors are becoming more familiar with the syndrome and how to recognize it, Chung said; he encourages providers and patients to consider POTS when symptoms include chronic fatigue, brain fog, severe palpitations, and sometimes gastrointestinal issues.
Dr. Sara Keller, also at Johns Hopkins, works with patients with conditions including chronic fatigue syndrome, fibromyalgia, dysautonomia, or irritable bowel syndrome. In the past year, she has seen people who've had COVID who are experiencing similar symptoms to those patients: fatigue, brain fog, memory problems, difficulty concentrating, and a fast or pounding heart rate, Keller told the Chronicle. "I wonder what people with long COVID might teach us about these other syndromes that have been around for a long time," she said.
As treatments are few for the conditions Keller's patients have, she mainly helps them manage their symptoms, she said. She told us it's important that her patients get enough rest, pace themselves, and not push too hard, although that is sometimes difficult for them to do, at least when it comes to returning to work. "Our social safety net around things like short-term disability is really failing a lot of people," she said. "They have to go back to work because they don't have a way to cover their bills otherwise."
Three Stories of Long COVID
Chest pain, heart palpitations, high blood pressure, headaches, blurry vision, insomnia, tremors, forgetfulness, laryngitis: These are just some of the serious problems 41-year-old Ashley Richardson, a nurse who cares for newborns and new moms at a local hospital, has lived with since her initial recovery from COVID-19. She became ill in early summer and felt "decent" for a couple of weeks after her quarantine period was over, she told us. But in July, her troubles reappeared and haven't stopped.
Richardson has been to the ER several times and has seen a constellation of specialists, including a cardiologist, neurologist, and ophthalmologist. Aside from being put on medicines to quell a huge spike in her blood pressure and to treat an irregular heartbeat, care for the symptoms that have developed since her illness has been scant. "I have the care and coordination between specialties, but there's just not a lot that everybody can do. There's not a lot of answers," Richardson said, adding that she felt like she was in "stagnant waters" in terms of her condition – not getting worse but not getting better.
Her long COVID symptoms came on in fits and starts. First, she noticed her blood pressure was way up and she felt her heart skipping beats. Later, she noticed her hands shaking so much it was hard to put her key in the door, and she was having serious memory problems – both frightening to her as a nurse and as a mom caring for a child with Type 1 diabetes. Vision problems, stuttering, and bouts of anxiety also emerged. More recently, she's developed bladder and bowel issues, she said, and has been suffering from lasting fatigue. After being off work for more than five months, Richardson now works one 12-hour shift per week, because it takes her three or four days to recover, she said.
"It just felt like it was sort of this domino effect – that, you know, two weeks after I was 'healed' per se, or out of quarantine, everything just kind of slowly started backsliding," she told us. "And one by one all of these weird symptoms just started popping up." As a health care professional herself, Richardson wants answers, but has gotten few; most tests come back normal, she said, deepening her frustration and continuing to puzzle her doctors, and ultimately leading her to join online support groups in hopes of learning more.
"I came to the realization ... that I was one of many obviously struggling with these symptoms," she said, "and just not really getting any clear answers, because there's not a clear-cut 'something' that shows up on a CT scan, or something that comes back abnormal in blood work. I feel like the more tests that they do, the more they all come back normal, which brings an even more frustrating piece to the puzzle."
In early March, Richardson told us by email that her symptoms have worsened. "I've now been officially diagnosed with autonomic dysfunction/POTS and have really been struggling with my fatigue, bone and joint pain, tremors, brain fog/memory issues, headaches, and stuttering pretty bad. I would love to say I'm better, but I've gotten so much worse," she wrote. "I'm trying to find a medical study to participate in and a COVID clinic to hopefully get more answers."
New Braunfels native Alice Navarro, 41, contracted the virus in June. In the run-up to her 10 days in the hospital, she mainly felt tired at first, but then had more difficulty breathing, she told the Chronicle. Navarro, who had mild asthma pre-COVID, found she was using her inhaler more and more, and eventually the rescue medicine was not having any effect. That, combined with a fever, spurred her to seek medical attention at her provider's office, where she was told she probably had COVID, but to go home. Another staffer at the clinic, who knew her as a patient, urged her to go to an emergency room instead, which turned out to be a lifesaver. Navarro was placed on oxygen and hospitalized; she was later told she could have died of sepsis over that weekend had she gone straight home.
In the months since her ordeal, Navarro has recovered, but not to the strength or fitness she had before. She has also developed sleep apnea and is on several additional medications to help her breathe, including one for chronic obstructive pulmonary disease or COPD, she said. Even so, she has asthma attacks much more frequently than before. "I have trouble leaving my apartment in the morning. When it's really cold, I can't even walk out the front door without having an asthma attack ... That's new!" she said.
In early March, Navarro told us that she is "still dealing with breathing issues through asthma and adjusting to sleeping with a CPAP machine [used to treat sleep apnea] at night," but considers herself to be doing "pretty well at the moment" and wrote that the experience with COVID has affected her in other ways. "I'm making an extra concerted effort to let my loved ones know that I love them," she wrote.
Jacqueline Gheorghe, now in Austin for an internship, also fell ill in June while visiting family in Washington state. The 30-year-old said she had fairly mild illness, but a few weeks after recovering from COVID, she was experiencing dizziness, lightheadedness, fainting, and extreme fatigue, she told the Chronicle. She also had difficulty understanding what people were saying and couldn't read for more than a month, and later noted some vision problems. Gheorghe was seen by various doctors, including a neurologist who diagnosed her with post-viral syndrome. In November, she traveled to Mexico and received stem cell therapy, which she believes greatly improved her condition. This type of therapy is regulated by the FDA in the U.S.; while there are some trials underway here exploring stem cell therapy to treat acute COVID-19, nothing has yet been approved. These days, Gheorghe's only ongoing symptoms are muscle spasms and cramps, she told us in an email in late February.
Struggling to Respond
In early November 2020, the Travis County Medical Society and UT's Dell Medical School hosted a town hall on long COVID. Panelist Dr. Rama Thyagarajan shared an overview of what was known then about the disease, calling it "a very complex and very serious and real medical illness." Thyagarajan is an assistant professor of internal medicine with Dell Med.
The prevalence of long COVID could be anywhere from 10% to 87% of those experiencing illness from COVID-19, Thyagarajan said. The wide range "tells us that the definitions are still not clear," she adds; the figures are based on data from surveys, social media support groups, and phone apps. Symptoms can come and go and impact the heart, lungs, nervous system, joints, digestive system, and ability to sleep, all without clear causes, she said. Thyagarajan urged physicians at the town hall to take long COVID patient complaints seriously, stating that "patients uniformly describe that the medical community is not receptive." Many patients also suffer with anxiety, depression, and post-traumatic stress, she said: "As health care providers, we have to acknowledge and support our patients."
CommUnityCare's Dr. Yagoda, while not skeptical that long COVID is real, shared his frustration with the Chronicle that the illness is difficult to diagnose because it's not medically well defined. There are no standard protocols to integrate into a differential diagnosis, he said, which makes it hard to know how many patients are long haulers. "The scope of the symptoms is pretty broad and not unique to COVID itself," he said. "We don't have a clear sense of whether post-COVID syndrome has any sort of characteristic features on a chest X-ray or characteristic lab findings. At this point there doesn't appear to be anything that you can hang your hat on with respect to diagnostics. This leaves providers to make a clinical diagnosis," Yagoda said, based on signs and symptoms rather than testing.
Some of Yagoda's long COVID patients had moderate COVID-19 symptoms initially, while at least one he could recall was only mildly ill. They are almost universally self-diagnosed, he said. "They are coming in, sometimes for routine follow-up but sometimes specifically for this concern, and fairly universally they say, 'The symptoms that I started with when I got sick have either not gone away or transformed into other things.'"
The result in many of these cases has been "constant suffering from the point of infection," he said. "In some ways, the prolonged sort of disability that these long symptoms cause is almost as taxing as those acute severe symptoms." He described one patient diagnosed with COVID-19 back in March who reports that she previously had a "photographic" memory. She "now is having to walk around with multiple sticky-note pads, and her house is covered in sticky notes," Yagoda said, because she otherwise can't remember the things necessary to function and work. Among many patients, "the feeling, the sensation that is universally stated, unsolicited, is 'I just don't feel all there anymore. I don't feel like myself anymore.' Which is a harrowing and heartbreaking thing to hear," he said.
Area health care systems were unable to provide many specifics about how they're responding to local long haulers. Austin Regional Clinic "does not have a formal COVID-19 long hauler program, but we encourage patients to follow up with their doctor if they have ongoing symptoms after COVID-19 infection," said Dr. Manish Naik, ARC's chief medical information officer, in an emailed statement. A spokesperson for Baylor Scott & White provided links to patient resources on the system's "Scrubbing In" discussion page. Ascension Seton and St. David's HealthCare both told us through spokespeople that they could provide no information regarding how many COVID-19 or post-COVID patients their respective hospitals have treated, nor whether any type of follow-up or post-COVID treatment is being offered.
An Austin Public Health spokesperson told the Chronicle in an email that the agency is "not tracking long haulers and we are not collaborating with any clinic in studying long haulers." Echoing CommUnityCare's Yagoda, APH added that one challenge to conducting surveillance for long haulers is the "lack of an established case definition from the [Centers for Disease Control and Prevention]" for the condition. Multiple sources told us that a post-COVID clinic is being set up under the leadership of Dr. Lucy Leykum at Dell Med, but a spokesperson said she would not be able to provide any details regarding the clinic until at least early April.
What the Survivors Know
After first appearing in humans as a severe respiratory disease, COVID-19 has turned out to be much more complex. We now know it can affect the nervous and cardiovascular systems of those infected in many different ways, from headaches and vision problems to "COVID toes." While the virus generally affects children less severely than adults, it infrequently produces a serious delayed immune system dysfunction known as multisystem inflammatory syndrome (in children, MIS-C; in adults, MIS-A). While having the illness or the vaccine provides significant levels of immunity, it's not yet certain how much or for how long; cases of multiple infections are considered rare but have occurred. This is all made even more complex and uncertain by the virus' continued mutations and known variants emerging around the globe.
Dell Med neurologist Dr. Melamed told the Chronicle that SARS-CoV-2 is "very smart" and can penetrate virtually any part of the body, potentially using one or more pathways into the brain and nervous system, in ways that researchers are still trying to understand. As she explained in an online "UT Brainstorms" talk in November, the virus is causing "mixed syndromes" that affect both the central and peripheral nervous systems, something neurologists don't normally see.
Dysautonomia and loss of taste, smell, or hearing involve the peripheral nervous system, while headaches, fever, weakness, and confusion can result from inflammation of the central nervous system, i.e., the brain and spinal cord. Post-COVID effects appearing in some adults include Type 1 diabetes and some cases of MIS-A, Melamed said. "It will be very important and interesting scientifically to define better why these autoimmune diseases are starting and [whether] they are transient ... or are these going to become longer-lasting complications of COVID that we really, as clinicians, have to think about when we see patients?"
Diana Berrent was an early COVID-19 case in the U.S., testing positive in early March 2020. The 46-year-old Long Island resident and mother of two went on to form Survivor Corps – part advocacy group, part support group, and part research hub for people affected by COVID, including long COVID. "We are partnering with leading scientists and doctors from around the world who are coming to us, because we have this vast set of data and this incredible membership of individuals who are also committed to giving back," Berrent told the Chronicle. The former lawyer and photographer started the group as a way to help science help survivors. "We had the power to actually help, in a moment where we were being told that there was nothing that you could do to help," she said.
The group, which currently has roughly 160,000 members, has been especially effective at collecting information from survivors who were never hospitalized – the "Tylenol and Gatorade variety," as Berrent calls them, who did not receive interferons, antivirals, steroids, or anticoagulants. "It's important to be looking at nonhospitalized patients," she said, "and not just assuming that we can extrapolate out from the data that we have on hospitalized patients."
Berrent cited one example of how her group has added to the national and global conversation: "We published a symptom list in July that generated probably a thousand articles and brought attention to a lot of symptoms." Survivor Corps' data was used to describe 98 symptoms of COVID at a point when the CDC had just increased its list of reported symptoms from four to 12, Berrent said. Another report using Survivors Corps data showed that fevers were actually not a common symptom for many of those infected with the coronavirus.
Natalie Lambert, an associate research professor at Indiana University School of Medicine, is the research director for Survivor Corps and has played a key role in these reports. Her research focuses on how people self-report their health problems and experiences, to determine which of their needs are not being met. When the pandemic hit, Lambert began reading patients' personal COVID stories online, and "it was really clear right away that the [CDC's] short list of symptoms ... was not a match for how many people were describing what it felt like to have COVID," she told us. This meant research was needed "right away" to understand how COVID was actually impacting people's health and to help ensure that future treatments or policies would truly meet people's needs.
Lambert said that, to date, she has analyzed more than 1 million Facebook posts from Survivor Corps members. A new, comprehensive Survivor Corps report is expected out this month based on more than 5,000 survey respondents with COVID-19 and post-COVID symptoms for more than 21 days. The report shows that fatigue, memory problems, and muscle aches have persisted as problems for many COVID survivors, Lambert said; brain pressure, vision problems, hearing problems, and ear pain are among the other reported symptoms that should be concerning to medical providers and the public. She is exploring if and how factors such as preexisting conditions, family history, and medication history may be involved in the experiences of long haulers.
Changing symptoms that come and go from day to day are themselves an identifiable symptom of long COVID. In information shared with us from Survivor Corps' upcoming report, more than 20% of survey respondents experienced changing symptoms, with many rating them as greatly impacting their ability to work. "Patients feel like they're six months into this and every morning, it's like waking up and reaching into a shopping bag and grabbing a handful of symptoms; you never know which ones they're going to be," Berrent told us. She believes that, as a country, we need to prepare for the "shadow pandemic" of long-term disability that COVID-19 may be creating, which includes finding effective treatment.
"There has not been nearly enough focus on treatment yet because our collective focus has been entirely on acts of prevention," Berrent said. To help fill that niche, Survivor Corps is currently working with a team of experts to create a blueprint of what a "gold standard" post-COVID care center should look like. Berrent also said the group's recent work suggests that vaccines may improve the symptoms of some long haulers. In addition, monoclonal antibody treatment is being made available to certain people newly diagnosed with COVID-19 through the group's website, she said.
For Austin's Ashley Richardson, new answers and better solutions can't come soon enough. "I'm not sure I will ever get back to 'normal' but I just want to be more than just functional," she told us in a recent email. "It would be awesome if the local medical community hears our cry for help and works together with their colleagues to have a meeting of the minds and figure this stuff out."
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