Prevention (USA)

In It for the Long Haul

Understand­ing postCOVID syndrome

- BY GINNY GRAVES

While it’s true that most people recover from COVID-19, a growing number continue to experience debilitati­ng symptoms months after the onset of their infections. Scientists are racing to find out why post-COVID syndrome happens and what we can do about it.

Last spring, as New York City hospitals were beginning to get a handle on the first onslaught of COVID-19 cases, doctors at Mount Sinai Health System noticed something unusual: Some COVID-19 patients were still experienci­ng symptoms weeks after their initial infections had passed. “They had issues like fatigue, brain fog, chest pain, shortness of breath, racing hearts, GI symptoms, and anxiety and depression,” says Joan Bosco, M.D., an internal medicine doctor at Mount Sinai. “It was surprising, because some of the least sick patients initially wound up being the sickest down the road.”

Today we call them “long-haulers,” people who suffer from a range of puzzling symptoms after a bout with the novel coronaviru­s, many for months on end. While some studies state that only patients who have had lingering symptoms for 12 weeks or more qualify as having post-COVID syndrome (PCS), many experts say anyone who has persistent symptoms four weeks after a COVID-19 infection should talk to a doctor. With the pandemic still not under control at the time of this writing, tens of thousands may be joining the ranks of those with PCS every month.

THE MANY FACES OF PCS

Estimates of how many COVID-19 patients go on to develop post-COVID syndrome vary from 2% to 25% or more.

Interestin­gly, PCS seems to affect more middle-aged adults than older ones, but as yet no one knows for certain why PCS happens or who is most likely to experience it. “That doesn’t mean it’s not real,” says Laurie Jacobs, M.D., an internist at the COVID Recovery Center at Hackensack Meridian Health in New Jersey. “Many of my post-COVID patients say their primary care doctors dismissed and disregarde­d their symptoms, which compounds their suffering.”

Shayna Zweiback, 27, of East Meadow, NY, was one such patient.

She fell ill with COVID-19 in March 2020. After recovering from her initial infection, she felt better for a couple of months, but then her health began to deteriorat­e rapidly.

“First I developed extreme fatigue and brain fog,” Zweiback says. “I’d forget what I was talking about in the middle of a conversati­on, I had trouble distinguis­hing between letters and numbers, and it took me a day to recover my energy from a walk down the block or a trip to the grocery store.” She also had serious shortness of breath. “It felt like air hunger,” she recalls.

Prior to the pandemic, Zweiback had suffered from depression, which was exacerbate­d by her physical health issues. Before she was treated at Mount Sinai in August, “everyone told me my depression was the cause of my postCOVID symptoms,” she says. “They made me feel like my illness was my fault.” Now she knows it’s that her physical symptoms are worsening her mental health, not the other way around. Mount Sinai launched the first multidisci­plinary post-COVID clinic last May to treat long-haulers and learn what works to help them. Now it can barely keep up with demand, and dozens of similar clinics and treatment programs have popped up across the country.

WHAT MAY BE GOING ON

SARS-CoV-2 (the novel coronaviru­s) isn’t the first virus to cause lasting symptoms, says Greg Vanichkach­orn, M.D., medical director of Mayo Clinic’s COVID Activity Rehabilita­tion Program. “Previous viral outbreaks, like SARS and MERS, left some people debilitate­d for months, sometimes years,” he says. “The virus isn’t still alive and active in people with ongoing symptoms, but it triggers a response in the body that causes these persistent symptoms. Now we’re trying to figure out what that response is, and we have some likely suspects.” These are:

EXCESS INFLAMMATI­ON

The leading candidate is immunesyst­em-related inflammati­on. “We see high levels of inflammati­on in many of our post-COVID patients,” says Christian Sandrock, M.D., a specialist in emerging infectious diseases at UC Davis Health in California who is treating patients at its post-COVID-19 clinic. In fact, when researcher­s in Europe did MRIs of the hearts of 100 people who had recently recovered from COVID-19,

they found that 60% had ongoing heart inflammati­on, which can cause some of the symptoms many long-haulers report, such as shortness of breath, chest pain, and elevated heart rate with exertion. What’s more, that inflammati­on affected people regardless of their preexistin­g conditions or how sick they were when they initially had the virus.

AN AUTOIMMUNE RESPONSE

For some long-haulers, COVID-19 might have triggered their immune systems to mistakenly target their bodies’ healthy tissue instead of the virus, says Dr. Vanichkach­orn. This is called an autoimmune response. Researcher­s at Yale University recently found that COVID-19 patients had large numbers of auto-antibodies (immune molecules that attack healthy tissue) compared with people without the virus. And autoimmune diseases such as lupus and rheumatoid arthritis commonly cause fatigue and digestive issues, two typical post-COVID symptoms. It may be that the same mechanisms behind those conditions are causing these symptoms in people with PCS.

PROBLEMS WITH THE NERVOUS SYSTEM

Many PCS patients show symptoms of dysautonom­ia, which refers to a dysregulat­ion of the autonomic nervous

system (responsibl­e for involuntar­y functions like blood pressure, heart rate, breathing, and digestion). “Dysautonom­ia affects blood flow, including blood flow to the brain, so it can cause fatigue, headaches, brain fog, and exercise intoleranc­e,” says Dr. Vanichkach­orn. “When we test patients with post-COVID syndrome, they often have some autonomic dysfunctio­n, so it’s probably a piece of the puzzle, at least for some people.”

BLOOD CLOTS AND BLOOD VESSEL DAMAGE

Tiny blood clots could be playing a role too. Many PCS patients have high levels of a protein in the blood that indicates that their blood is more prone to clotting. “When we put them on medication to prevent clotting, they feel better,” says Dr. Sandrock.

The likely reason COVID-19 patients frequently develop blood clots: The virus can infect and damage the cells lining the blood vessels, says William W. Li, M.D., medical director of the Angiogenes­is Foundation and one author of a recent COVID-19 study. This lining is ordinarily smooth and slippery, like an ice rink, says Dr. Li, which allows blood to flow easily. But when the endothelia­l cells lining the vessels become damaged, they get sticky, which causes platelets in the blood to adhere to the vessel wall, forming clots. “We’ve now examined tissue from people who died of COVID-19 and found widespread clots everywhere there were infected blood vessels—in the lungs, brain, heart, kidneys, and other organs,” says Dr. Li. “These tiny blood clots interrupt normal blood flow and damage organs. When they occur in the lungs, they can cause shortness of breath. Microclots in the heart may contribute to palpitatio­ns.” Damage to these cells lining the blood vessels has also been found in the brains and hearts of people with COVID-19 and may contribute to brain fog and cardiac damage, Dr. Li adds.

SO MANY SYMPTOMS

Since starting at the Mount Sinai clinic, Zweiback has seen eight specialist­s, from a cardiologi­st to a gastroente­rologist. She’s had MRIs, CT scans, and blood tests, which revealed high levels of inflammati­on. “The goal of treatment,” says Dr. Bosco, “is to identify underlying problems, get patients’ symptoms under control, and slowly improve their ability to function.” Zweiback is being treated for migraines, muscle pain, reflux, vitamin deficienci­es, panic attacks, and postural orthostati­c tachycardi­a syndrome, a blood circulatio­n disorder that makes her heart rate skyrocket when she walks. All those problems set in after her bout with COVID-19. Doctors are also helping Zweiback cope with her preexistin­g depression.

For many patients, however, mental health issues appear after a COVID-19 infection, according to a November study published in The Lancet Psychiatry. Anxiety and difficulty sleeping are among the top 10 most common symptoms, according to a survey of more than 1,500 long-haulers conducted by

the Indiana University School of Medicine and Survivor Corps, a grassroots coalition of COVID-19 survivors. Members of the corps track their symptoms and raise money for research in the hope of finding a cure.

HOW TO PROTECT YOURSELF

PCS is challengin­g, Dr. Vanichkach­orn says, because most patients have multiple symptoms—the Survivor Corps survey identified 98 possible ones. Dozens of studies of long-haulers are underway worldwide that will one day provide answers. “We’re essentiall­y building the plane while we’re flying it,” says Dr. Vanichkach­orn. Without clear answers right now, doctors who treat PCS say the best way to protect yourself is not to get COVID-19 in the first place. “This isn’t ‘just the flu,’ ” says Dr. Bosco. “People need to understand that there can be long-term consequenc­es from a COVID-19 infection and take all the precaution­s, including wearing a mask, washing hands, and social distancing.”

If you do get COVID-19, take plenty of time before jumping back into regular activities. “We know from SARS and chronic fatigue syndrome that if you push too hard, you experience a setback,” Dr. Vanichkach­orn says. Some of his PCS patients were marathon runners. “Now they count it as a victory to walk across the bedroom without feeling breathless. Recovery is slower than people would like, but we’re seeing gradual improvemen­t in most patients.”

Zweiback acknowledg­es that the slow progress can be frustratin­g, but as with everything else about this pandemic, she’s taking it one day at a time— avoiding stress, eating regular and healthy meals, and staying hydrated. “I’ve been sick for 13 months, and I’m probably 65% recovered,” she says. “If I’ve learned one thing, it’s that I have to pay attention to my body, rest when I’m feeling tired, and be patient.”

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