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What We Know and Don’t Know About Long COVID

More than a year into the pandemic, long COVID still confounds scientists.

By Madeleine Gregory
Jun 1, 2021 5:00 PMJun 1, 2021 5:10 PM
a nurse with long covid - shutterstock
(Credit: Supamotion/Shutterstock)


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Long COVID remains a mystery. We don’t know what causes it, how to treat it, and why some people recover while others don’t. 

But there are a lot of scientists working to answer those questions. As soon as COVID-19 was detected, the medical community switched into high gear: rapid tests were developed within weeks and vaccines were developed within a year. The rest of us learned how to recognize it (fever, fatigue) and how to avoid it (masks, social distancing). The pandemic response was far from perfect, but we knew the general shape of the disease: you got sick and you hoped to get better.

Except that many people didn’t get better.

Over a year into the pandemic, many researchers have shifted their focus from acute COVID-19 to “long COVID,” the phenomenon where people continue to have symptoms after the infection has gone. 

The names and definitions are still fuzzy. Most refer to it as “long COVID” or “long-haul COVID,” but at this point, it’s a syndrome rather than a defined illness. That means that it’s just a grouping of symptoms without a defined underlying cause, explained Daniel Chertow, a physician investigator who studies emerging infectious diseases at the National Institutes of Health (NIH). 

The symptoms of long COVID include fatigue, brain fog, and trouble breathing. Some patients have lingering pain or get dizzy when they stand too fast, and exercise often makes it worse. These symptoms signal some underlying biological impacts, and researchers are testing various theories about the potential causes. 

What Causes Long COVID? 

There are a number of theories about why long COVID happens, none of them fully confirmed. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke at the NIH, laid out some of them. The virus might hang around in the body, replicating and prolonging the infection. Or it may stick around but not replicate, stimulating biological responses. 

One of Chertow’s studies is investigating this theory. Since early in the pandemic, Chertow has been leading an autopsy study that looks at those who have died from COVID-19, sampling around 100 sites throughout the body. 

“One of the goals of the study is to investigate in a very detailed way exactly where throughout the human body and brain the virus goes, whether it is replicating and could be cultured, and how long it persists in those different compartments,” Chertow explained. 

He says that found inflammation and scarring throughout the body. They also, however, found areas where there was no evidence of tissue damage, but where there was evidence of the virus. Chertow says that means the virus can hide “in plain sight,” and gives credence to the idea that the virus hanging around could cause lasting symptoms. 

Another theory Koroshetz mentioned is that the immune system, revved up by the acute COVID infection, could be reacting to the patient’s own body, as it does in autoimmune diseases. Another possibility is that injuries to certain systems — such as the autonomic nervous system — could be causing symptoms such as lightheadedness and fast heart rate. Finally, COVID-induced tissue damage to the heart, kidney, brain or other organs could cause persistent symptoms.

At USC, Professor of Radiology Ali Gholamrezanezhad is investigating the latter theory: how tissue damage affects long-term health. His research is focused on those who were previously hospitalized for COVID-19, and uses high-tech imaging and exercise tests to look at how recovery is going.

In a lot of patients — even those who don’t have lingering symptoms— Gholamrezanezhad and his team find evidence of scarring and distortion of the lung tissue. 

Many of the theories about long COVID aren’t mutually exclusive — it could be a combination of various biological responses. Post-viral conditions are not entirely uncommon, and can cause similar symptoms: chronic fatigue, lingering pain. Historically, the treatment for these conditions has largely been managing symptoms. Some see COVID as an opportunity to learn more about post-viral conditions generally. 

“With COVID, you know exactly when the original infection happened, and you can study people through their recovery,” says Koroshetz. “Then, you can try and determine the difference between those who get better and those who don't.”

Congress has put $1.15 billion behind an NIH initiative to study the long-term consequences of COVID-19. The project includes research at hospitals across the country, collecting all the data centrally. Koroshetz says that the initiative hopes to find out enough about long COVID to develop interventions. 

Who Is Affected? 

Scientists are still grappling to understand how many people continue to have symptoms after acute COVID-19 infections. The overall number is somewhere between 2-10 percent, Koroshetz says. That jumps up to about 50 percent if you were hospitalized for COVID-19. For those who were in the ICU, it’s even greater: 80 percent. According to one CDC study, 35 percent of nonhospitalized COVID patients were still not back to their usual health after 3 weeks, but Koroshetz says that that number would likely be way down after a few months. 

Though there are disparities in who gets COVID based on race and socioeconomic class, they don’t seem to be statistically significant predictors of who will continue to suffer from long COVID, according to one study in Nature. However, researchers did find differences in susceptibility: older people are more likely to experience prolonged symptoms than younger ones, and females are slightly more likely to suffer from long COVID than men. 

Gholamrezanezhad says that, alongside age and the severity of the COVID case, preexisting conditions — such as diabetes, hypertension, heart disease, and immune conditions—can make patients more susceptible to scarring or long-term symptoms. That’s especially true of conditions that affect the lungs, such as asthma, COPD, and lung cancer. 

What Does Recovery Look Like? 

Currently, there is no treatment for long COVID. While researchers search for treatment options, managing symptoms is often the most that doctors and patients can do. Many are taking cues from the Chronic Fatigue Syndrome (CFS) community, which has been managing long-term fatigue for years. 

One study found increased use of opioids to manage the symptoms of long COVID, a practice which many doctors are discouraging and raising alarms about. The same study found increased prescriptions of antidepressants and anti-anxiety medication to address the mental health burden of long COVID. 

Paul Garner, a professor at Liverpool School of Tropical Medicine, has spoken out about the importance of centering recovery stories in our conversations about long COVID. He suffered from long COVID, and for a while believed he would never get better. 

“What happened to me just went on and on and on and I kept adjusting my time of recovery,” Garner says. “Two weeks, six months, by the end of the year. I went into a state of mind where I wondered whether I'd get better at all.”

But then he did get better. Accepting his illness and speaking with other people who had recovered from similar conditions paved the way for his recovery, he says. He’s sharing his story to give people hope: the impacts of long COVID are real and severe, but he wants people to know that recovery is possible. 

At this point, the best way to prevent long COVID is to prevent the disease. For those with COVID, Gholamrezanezhad emphasizes treating patients early—avoiding extreme measures like intubation can prevent some of the worst scarring. 

Researchers also advocate getting the vaccine, the best known protection against COVID-19. Chertow says that there is some anecdotal evidence that vaccines can alleviate symptoms of long COVID.

“The global population has in some form or another shifted their focus to COVID,” Chertow says. “We’ve got a ways to go, but I strongly believe that we will continue to get a better understanding of how long COVID works.”

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