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Nearly One-Third of COVID Survivors Have Lingering Symptoms, Study Finds

Nearly One-Third of COVID Survivors Have Lingering Symptoms, Study Finds

Scientists are working to understand why “long haulers” face months of sometimes debilitating symptoms. Here’s what we know.

Updated on February 23, 2021 at 11:00am EST.

Before Russell Frisby, a lawyer in the Washington, D.C. area, contracted COVID-19, he was healthy except for mild, well-controlled asthma, with an active lifestyle that included golf. In March 2020, Frisby was hospitalized for five days due to the coronavirus. He survived, but six months later he still experienced persistent symptoms.

At its peak, the illness wore away at his spirits.

“You’re sick. You don’t think you’re making any progress. You don’t know when it’s going to end or what it’s going to mean for your life,” Frisby recalls.

He’s not alone.

New research suggests that many people who’ve recovered from COVID-19 continue to experience symptoms months later—even those who had only mild infections.

A February 2021 study published online in JAMA Network Open found that nearly one-third of COVID-19 patients who were not sick enough to be hospitalized have lingering issues months later. Among the most common complaints: fatigue, loss of sense of smell or taste and brain fog.

For the study, University of Washington (UW) researchers surveyed 177 people between 31 and 300 days after they recovered from COVID-19. Nearly 85 percent of these patients had only mild illness. Most of the surveys were completed 210 days after becoming sick, or a median of 169 days later. Overall, 32.7 percent reported having at least one persistent symptom.

Although the study is small, it represents the longest follow-up to date among those who’ve recovered from the disease.

Researchers are searching for answers
While mild symptomatic cases of coronavirus infection may result in full recovery in about two weeks, some COVID-19 survivors, like Frisby, are ill for months.

Post-acute or chronic COVID-19, sometimes called “long COVID,” can saddle people with a number of symptoms that can drag on after the worst of the acute illness ends. These include ongoing fever, irregular heartbeat, cough, joint pain, “brain fog” and difficulty thinking, vertigo, ongoing anosmia (loss of the sense of smell) and skin rash.

The most common post-COVID symptoms seem to be trouble breathing and fatigue that can be debilitating. Some survivors sustain damage to the heart, lungs, kidneys and brain, and in some cases have new diagnoses, including high blood pressure.

“The virus is something that can have a prolonged impact on people’s quality of life, people’s ability to return to work and people’s ability to do the activities they always wanted to do,” says Sarath Raju, MD, MPH, a specialist in pulmonary medicine who is treating Frisby at the Johns Hopkins Post-Acute COVID-19 Team (PACT)—a multidisciplinary medical clinic treating COVID-19 survivors with ongoing medical needs related to the virus.

More than a year into the pandemic, these problems remain poorly understood.

Estimates of the prevalence of “long COVID” range from as low as 10 percent to as high as 87 percent of survivors, depending on the group of patients studied.

Authorities have not even agreed on how to define post-acute COVID-19 yet. One proposed definition includes symptoms lasting more than 3 weeks, while chronic COVID-19 has been defined as more than 12 weeks of symptoms.

Researchers are trying to understand the risk factors not only for severe COVID requiring ICU care, Dr. Raju says, but also for “a course that involves prolonged symptoms and a prolonged recovery” after a relatively mild initial illness.

There is precedent for the phenomenon, and early hints at an explanation. The novel coronavirus’s cousin—the coronavirus that causes SARS—is one of several viruses that have been linked to persistent symptoms, potentially due to long-term inflammation. And SARS-CoV-2, the coronavirus that causes COVID-19, targets the ACE2 receptor, which studs many cell types in the body and offers entry into multiple organs. Organ damage could contribute to ongoing symptoms.

For example, cells that support the olfactory nerve and help it function have ACE2 receptors, which make them vulnerable to the virus. So, when the coronavirus attacks those cells, it could also harm olfactory nerve cells or the nerve, itself. This could help explain not only why COVID-19 influences smell and taste but also why many people continue to experience a loss of their sense of smell or taste even after they’ve recovered.

Post-acute or chronic COVID-19 also bears a resemblance to myalgic encephalomyelitis, commonly known as chronic fatigue syndrome (ME/CFS). This disorder causes debilitating fatigue and has been linked to dysfunction in mitochondria—the cell’s powerhouses—and to immune system malfunction. Some ME/CFS cases have been linked to recent viral infection. Something similar could be going on with COVID-19 survivors.

Finding a path to recovery
When Frisby first experienced coronavirus infection, he developed asthma symptoms that didn’t respond to his usual treatments. After several days, he developed a fever, cough and trouble breathing. He spent five days in the hospital with COVID-19, though he did not need to be intubated.

About a week after going home from the hospital, Frisby again experienced what felt like a stubborn asthma flare. Though his repeat COVID-19 tests were negative, he needed multiple medications to manage his lung symptoms, including a nebulizer every few hours.

For months, Frisby says, “it was horrible.”

“You’re coughing, and you can barely move,” he says. “It’s not like you can do anything. You’re just there—you can barely get out of bed, and you’re feeling lousy, just overall.”

Some post-COVID patients develop new symptoms, Raju says. But others, like Frisby, experience worsened symptoms of preexisting well-controlled asthma—even after a relatively mild bout of COVID-19.

“We’ve seen patients who weren’t even hospitalized who still have residual shortness of breath,” Raju says. “It comes as a shock, I think, to still be dealing with these issues for a prolonged period of time.”

Reason for hope
It’s still uncertain what people recovering from “long COVID” may face long-term. Many wonder when, if ever, they can expect to resume their pre-illness level of function. Whether they are at higher risk for other chronic diseases is also unclear. And no one knows yet if having received certain treatments for severe COVID-19, such as monoclonal antibodies, render a person more or less likely to become a “long-hauler.”

In order to answer these and other questions, studies are underway that delve into the body’s reaction to the virus. Scientists will also follow survivors over time to learn as much as they can about the long-term effects of the disease.

Researchers have called for a multidisciplinary approach and a research focus at clinics like Raju’s that care for post-COVID patients.

Frisby says he started to turn the corner in July 2020. A few months later in September, he said he felt “95 percent better,” noting that he still gets tired earlier in the evening. Beyond that, he says he’s doing okay.

Still, in the wake of his bout with COVID-19, Frisby now needs to take more asthma medications than he did before. And tests of his post-COVID lung function showed impairment, Raju said, which presents another mystery.

“His lung function may go back to normal over time,” Raju says. “But I think that’s still something we’re working to understand.”

Medically reviewed in February 2021.

Sources:
Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(2):e210830
Chen M, Shen W, Rowan NR, et al. Elevated ACE2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication. Preprint. bioRxiv. 2020.05.08.084996.
UpToDate from Wolters Kluwer. “Coronavirus disease 2019 (COVID-19): Clinical features.” Oct 6, 2020.
Science. “From ‘brain fog’ to heart damage, COVID-19’s lingering problems alarm scientists.” Jul 31, 2020.
del Rio C, Collins LF, Malani P. “Long-term Health Consequences of COVID-19.” JAMA. Published online October 05, 2020.
Nature. “The lasting misery of coronavirus long-haulers.” Sept 14. 2020.
Sweetman E, Kleffmann T, Edgar C, de Lange M, Vallings R, Tate W. “A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction.” J Transl Med. 2020 Sep 24;18(1):365.
UpToDate.com. “Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.” Sept 7, 2020.

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