'We just had no answers': COVID-19 'long-haulers' still learning why they're sick

Recurrent fevers, persistent constipation or diarrhea, intense bouts of fatigue, debilitating brain fog and vivid hallucinations — some people who catch COVID-19 experience symptoms like these for months on end, and we're still learning why that is.

Data gathered early in the pandemic suggested that most people with COVID-19 recover within a few weeks, if they survive the illness. But around April, stories began surfacing from those who remained sick for months after their initial symptoms emerged. Many of these individuals came together online to form support groups, with some referring to themselves "COVID long-haulers."

Now, six months since the World Health Organization declared COVID-19 a pandemic, formal studies of long-haulers are only just getting off the ground. But patients aren't waiting for science to catch up; they are organizing to collect data on their symptoms, tie those symptoms to biological explanations, and even to share potential — and unapproved — treatments. Knowing whether any of those treatments can alleviate the long-lasting symptoms of COVID-19, however, will take a more systematic approach and clinical trials, experts told Live Science.

A wide array of symptoms

One of the biggest ways long-haulers have expanded knowledge of the condition is by thoroughly cataloguing their symptoms. A patient-led research group, born out of the Body Politic COVID-19 Support Group, published the results of a survey of long-haulers in May that detailed some of their most common symptoms.

"At the time, we just had no answers," said Hannah Davis, a composer, independent researcher and core member of the Patient-Led Research for COVID-19 team. Davis began experiencing symptoms of COVID-19 on March 25, and to this day, many of her primary symptoms are neurological, she said.

"My first symptom was that I couldn't read a text message," Davis told Live Science, and she said her most persistent symptom has been "brain fog," or general cognitive dysfunction and trouble concentrating. In the May survey, nearly 70% of the 640 respondents reported experiencing either brain fog, insomnia or concentration issues, making these symptoms as common as a cough among long-haulers. A smaller percentage reported memory loss, dizziness, involuntary tremors, numbness in their extremities or hallucinations.

It's unknown whether neurological symptoms like these mostly arise from increased inflammation in the body or from the coronavirus directly infecting brain cells, though there's evidence for both, Live Science previously reported.

In addition to brain fog, many of the survey participants reported shortness of breath, tightness in the chest, fatigue, chills, body aches and a slightly elevated temperature, between 98.8 degrees Fahrenheit (37.1 degrees Celsius) and 100 F (37.7 C). Some less common symptoms included high fevers and severe gastrointestinal issues, such as constipation lasting for weeks, bowel obstructions and diarrhea leading to rapid weight loss. Long-haulers also reported seizures, migraines, vision changes, sensitivity to light and phantom smells, or smelling things that aren't there.

"For me, I've definitely experienced at least 100 symptoms over the last five months," Davis said. "People call it a 'grab bag,'" because some symptoms persist for many months while others seem to randomly crop up then disappear, she said. For instance, while brain fog remains her main symptom, Davis said she had transient rib pain, phantom smells and even vivid hallucinations that lasted a day or two, then went away.

Chronic fatigue?

"Long COVID is a whole spectrum of different conditions," said Paul Garner, a professor at the School of Tropical Medicine in Liverpool, England, who also developed his initial COVID-19 symptoms in March. But one common refrain is a sense of overwhelming fatigue.

Garner is among long-haulers who experience such fatigue as one of their main symptoms; some have compared the condition to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the exact cause of which is unknown.

When dealing with a new chronic illness, it's difficult to know what activities will trigger symptoms, Garner said. "You don’t know the speed limit and you don’t know when the penalties will arrive. You find out that when they do they are harsh, stopping you in your tracks for days," he wrote in a blog post published in June in The British Medical Journal Opinion.

He said he's learned that ample rest and keeping a decent diet helps keep his symptoms at bay, while physical activity and consuming alcohol can set them off. Similarly, 89% of respondents to the patient-led survey reported experiencing relapses in their symptoms, sometimes set off by exercise, stress, caffeine, alcohol or heat.

In the case of the fatigue she's experienced after contracting COVID-19, the sensation doesn't set in like typical tiredness, which comes on gradually, Dr. Mady Hornig, a physician-scientist at the Columbia University Mailman School of Public Health, told Live Science. "From my own experience, it's more like you're an electrical device and every once in a while someone pulls out the plug," she said. Hornig developed symptoms of COVID-19, including a fever and cough, back in April. Now, "I've had to be on a toddler's time table with self-enforced rest," she said.

But could a COVID-19 infection really trigger the onset of ME/CFS? Hornig said it's possible, given that other viral infections have been linked to the syndrome. For instance, an estimated 10% to 12% of people with infectious mono, caused by the Epstein-Barr virus, later develop a chronic course of ME/CFS, she said. (This increased risk is associated with symptomatic mono, according to a commentary in The Journal of Infectious Disease; most people carry the Epstein-Barr virus without developing any symptoms of illness.) Hornig said that she expects that, similarly, a percentage of patients who catch COVID-19 may go on to develop ME/CFS.

Hornig is now leading a study of "post-COVID phenomena" at Columbia to determine whether and how many long-haulers develop ME/CFS, as well as what other conditions crop up after the initial infection subsides. She also wants to track whether any long-haulers eventually stop experiencing symptoms; blood or tissue samples from these people could hint at what helps the body "bounce back" after prolonged illness, she said.

One of the major challenges in devising such studies is deciding what "post-COVID" really means, Hornig noted. "What is post-COVID? … The before and after becomes very blurry," she said. The acute, or short-term, phase of an infection is typically defined by characteristic symptoms that appear in a particular order, she said. But with COVID-19 patients, the initial symptoms vary person to person, and some people don't experience any overt symptoms, like cough or fever, but still go on to develop signs of organ damage.

"We still have much to learn about the variations in the onset, symptoms, signs and time to resolution of the acute disease, let alone what clinical symptoms or biomarkers might help predict long-term persistence of illness," Hornig said.

Hornig's research group is collaborating with the ME/CFS focused nonprofit Solve ME to develop a symptom tracking app for long-haulers, with the goal of tracking their symptoms over time and matching them up with patients' verifiable medical records. They are using data from long-hauler surveys, including ones conducted by the advocacy group Survivor Corps, to craft their survey questions. The medical records help confirm that when a patient reports experiencing brain inflammation, for example, brain scans back that up.

Dealing with doctors

The Patient-Led Research group is also launching a new project in conjunction with University College London. Their second survey will cover the first seven months of symptoms and ask about antibody test results, as some long-haulers don't test positive for antibodies when assessed, Davis said. This can become a sticking point when long-haulers seek medical care for their symptoms, because many never had a diagnostic test for COVID-19 when they first fell ill, she added. Therefore, antibodies would provide the only medical proof that they caught the virus at all.

In the U.S. "in March, April, you were only able to get a test if you were hospitalized. And most long-haulers are not hospitalized," Davis said. Even when long-haulers could get a diagnostic test, some got tested too late in the course of their illness, she said.

To account for that, the first patient-led survey included all symptomatic people, regardless of whether they had a positive COVID-19 diagnostic test or not. And their results indirectly support the notion that long-haulers without a positive test likely had COVID-19.The main difference between people who tested positive and those who tested negative was when they received their test. On average, positive people got tested on day 10 after developing symptoms, while negative people got tested on day 16. The diagnostic tests work by detecting bits of viral genetic material, and are more likely to give false-negatives once the body has had time to fight off the infection and the amount of virus in their body decreases, Live Science previously reported.

Requiring a positive diagnostic or antibody test poses a problem for many people seeking treatment for long-COVID. "Many post-COVID clinics require positive tests to be admitted," Davis said. "Diagnostic tests need to be deprioritized … Clinical diagnoses have to be enough," meaning long-haulers should be admitted based on what symptoms they show, she said.

She noted that, because long-haulers experience such a wide range of symptoms, patients should also receive a "full workup" of medical screenings, from pulmonary to cardiovascular to neurological.

Long-haulers all over the world have shared stories of doctors not believing that they had had COVID-19, and brushing off their symptoms as psychiatric in origin, Garner noted. "People were going in and being diagnosed with anxiety; it was appalling," he said. Hornig, a physician and psychiatrist herself, also encountered doubt from her health care providers when she tested negative for COVID-19 and for antibodies against the virus, she told Stat News in August. But she also tested negative for 12 other respiratory pathogens, including influenza, and based on her symptoms and the course of her disease, COVID-19 was the best explanation for why she fell ill, she said.

When seeing a doctor about persistent COVID-19 symptoms it may help to come prepared with documents describing your medical history, timeline of COVID-19 symptoms and the top questions you have for them, JD Davids, a writer, strategist and contributor to the Patient-Led Research survey, told Live Science in an email. It also helps to understand the medical practice inside and out, such as how long you might wait to see a specialist and who to call with insurance problems, he said.

Promising treatments, potential pitfalls

As a long-time advocate for people with chronic health conditions like HIV/AIDS and ME/CFS, Davids said that the lack of support long-haulers face reflects a historic trend in how health care providers treat those with chronic conditions. That's why patient-led groups play such a vital role in gathering information about their disease and potential treatment options, he said. Earlier in the year, Davids helped organize a webinar for people already living with chronic illness called "COVID-19 (Coronavirus) Preparation for People Living with Chronic Illnesses in the U.S.," to provide guidance for those who might face a heightened risk of severe disease, prolonged symptoms or death from COVID-19.

"These social networks are very fast at learning … medical science communicates through long, rather boring papers that take months of preparation," Garner said.

The speed of information spread in social networks can also mean speculative or untested treatments become widely known very quickly. For instance, some long-haulers say they have benefited from taking the heartburn medication famotidine, better known by the brand name Pepcid, Davis said. Specifically, they say the drug seems to ease their shortness of breath and reduce brain fog.