Long-haulers and the lingering effects of COVID-19

Some recovered patients experience a range of symptoms for months, baffling doctors

Julie Hakim, M.D., does not get knocked down easily. A pediatric gynecologist and research lab leader at Texas Children’s Hospital by day and a boxer and entrepreneur by night, she knows how to take life’s punches and get back up. But COVID-19 was unlike anything she had ever faced.

“I’m not someone who rests a lot. My life is 150 miles an hour from 4 a.m. to 9:30 p.m., just go, go, go,” said Hakim, a fit 40-year-old who cofounded FemTech Focus, a nonprofit designed to empower technology that improves women’s health and wellness. “But I couldn’t leave my bed. I would get up from my bed and go to one couch to the other couch. That’s all I could do. I was in tears on and off during the day.”

Although she was never hospitalized, she experienced the entire gamut of COVID-19 symptoms in what she called “one of the Top 3 worst physical experiences of my life.”

Hakim tested negative July 22, but she continued to feel crippling fatigue and joint pain.

“I was still profoundly fatigued, but it was a big improvement from constant tears of fatigue to just tears in the afternoon,” Hakim said. “I was slowly getting better, but it took a long time.”

One day, after she tested negative, she ventured outside for a walk and some fresh air. One block and 10 minutes later, she felt her legs teeter beneath her. She struggled to take another step and had to sit down on her neighbor’s front lawn—crying from sheer exhaustion.

“It was terrible. I would walk a block or three blocks and I would just be completely depleted,” Hakim said. “I was completely destroyed. I would run out of gas. I didn’t have anything in me. It was like you worked out for four hours and your legs were shaky. I just couldn’t do anything.”

The fatigue, joint pain, brain fog and headaches had persisted for more than a month.

Not like the flu

Hakim is one of thousands of COVID-19 patients across the country dubbed “long-haulers” who continue to experience a range of symptoms even after testing negative for the illness. It’s an apt name, given that recovery from the symptoms is taking much longer than expected for a growing number of people.

Patients who have been hospitalized with severe cases of COVID-19 face a long, hard road to recovery as it is, especially those who required mechanical ventilation. However, even patients with mild cases of the disease can find themselves managing symptoms for weeks to months—damaging their quality of life and productivity.

“We’re discovering more and more subacute and chronic complications of the infection, so it’s not just like the flu, where you get it for a few days and then you’re over it,” said Richard Robbins, M.D., chairman of the department of medicine at Houston Methodist Hospital.

The Centers for Disease Control and Prevention published a report in July that showed that 35 percent of 292 non-hospitalized COVID-19 patients continued to experience symptoms—such as cough, fatigue and shortness of breath—up to three weeks after diagnosis, whereas 90 percent of influenza patients fully recover and regain functionality within two weeks of a positive test result.

For some, it can take six weeks or months to recover, according to the Body Politic COVID-19 Support Group, which surveyed 640 long-haulers between April 21 and May 2.

To make matters worse, the spectrum of post-infection sequelae is seemingly endless. It’s a veritable mixed bag of symptoms, with people most commonly reporting cough, fever and shortness of breath. On top of fatigue, chills, sweats, body aches, headaches and difficulty concentrating, symptoms can appear in other parts of the body, including the brain, gastrointestinal tract, heart and skin.

“Consider it like a cluster bomb exploding in your body, having a ripple effect throughout your organs,” said Khurram Nasir, M.D., a preventive cardiologist at Houston Methodist Hospital.

In another survey conducted by Indiana University School of Medicine, approximately 1,500 members of Survivor Corps, a COVID-19 support group, reported 98 different symptoms—ranging from tachycardia to neuropathy in the hands and feet to tinnitus.

“There are certain diseases over the last century that have protean manifestations,” Robbins said, explaining that the word ‘protean’ comes from the Greek god, Proteus, who could assume whatever shape he wanted. “Diseases like syphilis or lupus can pop up in different organs and cause trouble, and this may be one of them.”

Raising awareness

The exact pathology of COVID-19 is still largely unknown. There’s a paucity of information about why post-infection symptoms of a respiratory disease continue to ravage people’s organs, but as more long-haul patients join online support and research groups in a grassroots effort to raise awareness, experts are formulating their best guesses to explain this mysterious syndrome.

“What we know is that the virus is cleared at that point, but the inflammation and the host immune response may have caused changes in those areas where the symptoms are still happening,” said Jill Weatherhead, M.D., assistant professor of tropical medicine and infectious diseases at Baylor College of Medicine. “For example, there could be inflammation within the lungs that’s causing someone to keep coughing.”

Inflammation, the immune system’s defense mechanism to protect and heal the body, requires a Goldilocks approach to be effective: not too much, not too little, just enough. But, as doctors are learning, these inflammatory responses can trigger a series of other changes in the body.

Emerging research also points to platelet activation as being a potential culprit. One study showed that SARS-CoV-2, the virus that causes COVID-19, induces changes to the gene expression of platelets and can lead to impairments in blood vessels.

“The endothelial cells [in blood vessels] experience dysfunction or are attacked, and it leads to platelet activation and coagulation pathways,” Nasir explained. “What they found is that each and every organ then experiences microthrombi [small blood clots], which block the smaller vessels that eventually leads to the cascade of localized inflammation, micro hemorrhages and bleeding.”

This is one area of study that could reveal why COVID-19 affects more than the lungs.

“What we are now seeing is that it affects each and every organ,” Nasir added.

More questions than answers

Julie Hakim has finally regained her strength, but she is left wondering about all the other long-haulers.

“It’s a very fascinating thing about how different people respond … to an immune challenge,” she said. “Some people are able to pass through it like it’s no big deal and other people have a huge inflammatory reaction.”

At the moment, because there are more questions than answers, doctors can only treat the enduring symptoms of COVID-19, not the underlying cause.

“There are a lot of different areas to be looking at in terms of what symptoms patients could develop and what type of long-term sequelae they could have from this,” Weatherhead said. “We don’t know who’s going to develop what. There’s just so much we don’t know yet about the disease to make predictions.”

One of the many unanswered questions for doctors: What are the long-term health effects of persistent COVID-19 symptoms?

“We have our eyes wide open looking for any [information] we can find,” said Robbins, who is developing an outpatient COVID-19 recovery group at Houston Methodist.

The multidisciplinary recovery clinic will be dedicated specifically to long-haulers. Slated to open in early October, the clinic will be staffed with 35 subspecialists—including cardiologists, gastroenterologists, infectious disease specialists, rheumatologist and neurologists—to treat, track and study patients over several years.

“Our job is to not just say, ‘OK, if you feel well, you’re fine,’” Robbins said. “We want to take people with even minimal symptoms and do formal follow-ups with biomarkers, imaging studies to see if we can predict or identify early people who might have some chronic problems with their kidneys, their livers, their brain, their heart, their lungs.”

What is clear, Nasir added, is that more work needs to be done.

“We have a superficial idea—but we don’t have an in-depth idea—of what recovery looks like,” he said.

For now, doctors encourage long-haulers to rest, recover and be patient.

“We’re learning a lot at a very rapid pace, but we’re also a culture of wanting to know everything right now,” Weatherhead said. “The scientific process to figure out what’s going on … takes time.”