Two years after the first COVID-19 patients raised alarms that symptoms could last for months, it’s clear the phenomenon is common — but medical experts still don’t know much about what causes it or how to treat it.

A study from the Centers for Disease Control and Prevention looking at 353,000 COVID-19 survivors found that about one in four who are 65 or older and one in five adults younger than 65 developed a new health condition that could be related to their bout with the virus.

There’s not much data about why some people are stuck with symptoms months after most COVID-19 patients have recovered, or when they might expect to feel better, though.

Diagnosing what’s become known as long COVID is mostly a process of ruling out everything else that could be causing a patient’s symptoms, said Dr. Thomas Campbell, a professor of medicine at the University of Colorado School of Medicine and chief clinical research officer at UCHealth.

The most common reasons that patients seek care at UCHealth’s long COVID clinic are fatigue and respiratory symptoms like persistent coughing or shortness of breath — all symptoms that can have many causes, he said.

“It’s not black and white at all,” Campbell said.

It’s not unexpected for people who were sick enough to be treated in an intensive-care unit to have lingering symptoms both from the medical condition itself and from the measures needed to save their lives, such as spending time on a ventilator. Other viruses can also cause prolonged symptoms in people who were mildly ill, but the phenomenon is more common with COVID-19. It’s also unusual to see so many different symptoms.

It still appears women are more likely to have long COVID, but it’s possible that could reflect differences in who seeks care, Campbell said. Data from the United Kingdom found the same gender difference, though the American and British studies disagree on whether risk rises with age, or peaks between 50 and 69. The British data didn’t include people living in nursing homes, which may have caused it to underestimate how many people over 70 were affected.

For now, treatment still focuses on addressing specific symptoms, like giving patients medicine to reduce coughing, and gradually building up their strength and endurance through physical therapy, Campbell said. Most patients start feeling better in three or four months, but people who were less healthy before getting the virus or became severely ill from the virus can take longer, he said.

There’s still a process of trial and error for medications, but evidence seems to be growing for a process of increasing people’s activity levels extremely slowly, said Dr. Tod Olin, director of the Exercise and Performance Breathing Center at National Jewish Health in Denver. It’s annoying for people who are accustomed to more strenuous exercise, but overdoing it seems to wipe out much of the progress patients have made, he said.

The National Institutes of Health recently started a study, called RECOVER, to understand why some people develop long COVID symptoms and others don’t, Campbell said. People who had COVID-19 and want to participate can email [email protected].

“To effectively treat long COVID, we have to understand it,” he said. “Otherwise, it’s just making guesses.”

One cause or several?

Olin said he and his colleagues have observed three general types of long COVID patients: people with excessive fatigue and shortness of breath; those whose heart rates spike erratically, causing them to get lightheaded from even slight activity; and those who have “brain fog.”

There are many other post-COVID symptoms, but those tend to be the ones that drive people to seek care, he said.

It’s too early to know if those are three presentations of one disorder, or distinct syndromes with different underlying causes, Olin said.

The CDC researchers looked at 26 conditions affecting the heart, lungs, kidneys, blood vessels, digestive system, brain and muscular system. While the risk for almost all of the conditions was higher in people who’d had COVID-19, the odds of developing a new respiratory condition were especially high.

The study didn’t prove the virus caused all of those conditions, since it’s possible doctors were looking more closely for other problems in patients who’d had COVID-19, or that some people had a condition before they got the virus and were only diagnosed after.

Some researchers think long COVID could be caused by an immune response gone awry, while others think fragments of the virus could be lurking somewhere in the body, keeping it in a chronic state of inflammation. Some think both could be correct, and that some patients could be dealing with still another underlying problem.

Researchers at National Jewish also found that in patients reporting excessive fatigue, cells didn’t seem to be using the available energy well. It’s an intriguing finding, since they typically only see that pattern in people with certain rare diseases, but it’s far too early to say that’s what is causing long COVID, Olin said.

“It’s a really preliminary signal,” he said.

Vaccines help — but how much?

A study looking at people treated by the U.S. Department of Veterans Affairs found that those who had been vaccinated and experienced a breakthrough infection were still at an increased risk of multiple health conditions, compared to those who didn’t have COVID-19.

They were better off than people who weren’t vaccinated before they got sick, with about a 15% lower risk of post-COVID symptoms — less protection than earlier studies had suggested vaccinated people might expect.

Like the CDC effort, the VA study was conducted before omicron took over and before booster shots were widespread, which may affect the results.

Dr. Zizad Al-Aly, chief of research and development at the VA St. Louis Health Care System, said it’s not entirely surprising that vaccinated people weren’t completely protected, because the shots were developed to prevent severe illness and death. Asking the vaccines to prevent a different syndrome is like expecting someone who trained for years as a sprinter to excel in a marathon, he said.

“They were never designed to protect us from long COVID,” he said.

The benefits were more significant for some conditions. Vaccinated people were about half as likely to develop blood clotting disorders as those who were unvaccinated, and their odds of severe lung problems also were significantly lower, Al-Aly said. It’s not completely clear why the level of protection is different, but it might reflect that vaccinated people are less likely to develop severe COVID-19, which involves lung damage and abnormal clotting, he said.

“It may be a carry-through effect,” he said.

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