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  • Recent studies show that coronavirus infection can cause long-term symptoms affecting multiple organs.
  • Shortness of breath, fatigue, and “brain fog” are among the most common symptoms of long COVID.
  • Research into the mechanisms of long COVID and possible treatments is ongoing.

Infection with the novel coronavirus could lead to long-term problems in the small airways of the lungs, even in people who had a mild infection, say researchers.

This adds to a growing list of lingering symptoms and complications that can occur after coronavirus infection — known collectively as long COVID.

Shortness of breath, fatigue, and “brain fog” are among the most common symptoms of long COVID.

For some people, symptoms continue after their initial infection. For others, complications may appear weeks or months later.

Research into the mechanisms of long COVID and possible treatments are ongoing.

In another recent study, a separate group of researchers examined the effect that coronavirus infection has on the brain. And other researchers are testing new treatments for heart-related symptoms of long COVID.

In a study published March 15 in the journal Radiology, researchers used CT imaging to examine the lungs of 100 adults who had COVID-19 and continued to have symptoms for at least 30 days after their diagnosis.

Researchers compared the CT findings of these participants with those from a group of 106 healthy participants.

Participants who had COVID-19 — even if not hospitalized for it — were more likely to have signs of damage in the small airways of the lungs compared with healthy participants.

“There is some disease happening in the small airways independent of the severity of COVID-19,” study author Dr. Alejandro P. Comellas, a pulmonologist and professor of internal medicine at the Carver College of Medicine at the University of Iowa, said in a news release. “We need to investigate further to see whether it is transient or more permanent.”

The COVID-19 group included 67 people who were never hospitalized, 17 who were hospitalized but not in the intensive care unit, and 16 who were treated in the ICU.

The most common symptoms in people with long COVID were difficulty breathing, fatigue, and cough.

Among the hospitalized group, almost 35 percent showed signs of air trapping in their lungs on their CT scans, compared with 7.2 percent of the healthy participants.

Around 25 percent of participants who had a coronavirus infection but weren’t hospitalized had signs of air trapping.

Air trapping is a condition in which people are not able to completely empty their lungs when they breathe out. This occurs in chronic obstructive pulmonary disease (COPD), asthma, and other obstructive airway diseases.

Of the nine people who had a CT scan done more than 200 days after their COVID-19 diagnosis, eight still had air trapping in their lungs.

A separate analysis of the CT images showed evidence of small airways disease related to ongoing inflammation in the lungs or fibrosis. The latter is a condition in which the lung tissue becomes damaged and scarred.

Researchers will continue to follow the participants to see whether their lung function improves or if symptoms persist.

“If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it,” Comellas said.

“It could be something related to inflammation that’s reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease,” he said.

“Brain fog” is another common symptom of long COVID, but it’s not the only neurological symptom people experience.

A study published March 2021 by researchers at the Northwestern University Feinberg School of Medicine found that people with long COVID also reported having headache, numbness or tingling, loss of sense of smell or taste, muscle pain, and anxiety or depression.

Barbara Hanson, PhD, a researcher at the Ken & Ruth Davee Department of Neurology at the Northwestern University Feinberg School of Medicine, said the severity of neurological complications seen with long COVID varies.

“We have some patients who seem severely debilitated by their symptoms, especially the cognitive symptoms,” Hanson said. “We’ve had some patients who have difficulty writing and reading, maintaining schedules, and working the jobs that they previously had.”

“Then there are others who may just feel a little fatigued. While some of that could be cognitive symptoms showing up, it mostly just presents as fatigue,” she added.

As with other symptoms of long COVID, Hanson said neurological complications can occur in people who only had a relatively mild initial infection, meaning they were not hospitalized.

“The experience of long COVID is not dependent on any of the symptoms at the beginning of the acute infection,” she said.

This was the case in a study that Hanson and her colleagues published March 7 in the journal Neurology: Neuroimmunology & Neuroinflammation.

“People who had mild to moderate COVID-19 had exactly the same outcomes [as people with more severe COVID-19] when they developed long COVID,” she said. “In fact, they had a greater number of symptoms and they had the subjective experience that they have not gotten better.”

In this study, researchers measured certain biomarkers related to the health of the brain, including one that indicates there has been damage to neurons.

Another biomarker shows activation of supporting cells in the brain known as “glial cells.” These cells are elevated in multiple sclerosis and other diseases of the brain.

Researchers combined these biomarker measures to come up with a “neuroglial score.”

The study had 64 participants, which included people hospitalized for COVID-19 who had an acute brain dysfunction known as encephalopathy, people with long COVID who had never been hospitalized for COVID-19, and healthy people from the community.

Researchers found that the neuroglial score correlated with anxiety in people with long COVID — people with symptoms of anxiety had a higher neuroglial score.

This association held up when the researchers took into account a participant’s age, sex, and body mass index, as well as when researchers used different measures of anxiety.

Hanson said this suggests there is a “true relationship” between the two.

For people with long COVID, their symptoms are very real to them. But because long COVID is not just one illness but many separate conditions, people may have difficulty getting an accurate diagnosis.

Being able to point to a biomarker that is correlated with a symptom of long COVID such as anxiety may offer some level of comfort.

“It is very validating to have biological backup that shows, ‘Yes, we can see from markers in your blood that it looks as if you are likely experiencing anxiety as a result of long COVID,” said Hanson.

However, she cautions that these biomarkers are not currently a “test” for long COVID. Still, she says they provide more insight into one aspect of long COVID.

The Centers for Disease Control and Prevention (CDC) estimates that between 5 and 80 percent of people develop long-term symptoms after coronavirus infection.

This wide range is due in part to a lack of long-term studies and a lack of agreement over how to define and diagnose long COVID.

However, many studies continue to show that certain symptoms are more common in long COVID.

A recent study published in JAMA Network Open found that people who were hospitalized for COVID-19 were more likely to have shortness of breath, fatigue, type 2 diabetes, and heart rhythm problems than people who didn’t test positive for COVID-19.

Dr. David B. Landers, an interventional cardiologist with Hackensack Meridian Health’s Hackensack University Medical Center, said fast heart rate, shortness of breath, and fatigue are the major symptoms in long COVID patients that he sees in his clinic.

“There is a wide range of severity,” he said. “Some people can’t walk 100 feet, and other people have symptoms intermittently, such as only when they’re doing something that requires a great deal of exertion.”

While some of his patients had severe illness with their initial coronavirus infection, others only had mild symptoms.

And by mild, he means people were not hospitalized for COVID-19. They may, however, have felt very sick during their initial infection, with symptoms such as headaches, fatigue, cough, and nasal congestion.

In addition, “we’ve seen a number of cases in which the patient was asymptomatic,” Landers said. “But their symptoms are so terribly consistent with long COVID that we believe, in fact, that they had a coronavirus infection which was largely asymptomatic.”

Landers and his colleagues recently started enrolling people into a study that is evaluating the use of beta-blockers as a treatment for long COVID. This class of drugs can lower the stress on the heart and blood vessels.

While he said these drugs seem to produce improvement in long COVID patients in his clinic, the study will measure these improvements in a more structured fashion.

“This will allow us to say with a greater level of a surety that the beta-blocker is working,” he said.

As scientists learn more about long COVID and more treatment studies are conducted, people with long COVID will have more options to help them get better.

For some people, given enough time and proper medical support, their outlook is good.

“There are a lot of people that are suffering from this syndrome,” said Landers. “But we can offer some encouragement, in the sense that many people tend to get better over time.”