Scientists report that brain scans of long COVID patients show abnormal activity in areas related to memory.

The scan results validate the concerns of these patients, who feel like they’re experiencing fatigue, trouble concentrating and memory issues, even though their scores on thinking tests don’t show it.

“We were able to show that even though they were able to do the task — they did everything correctly — the brain was functioning in a way that shows that it’s compensating,” said lead researcher Dr. Linda Chang, a neurologist at the University of Maryland School of Medicine. “The brain actually is using different parts of the brain to do the work. That means the normal brain network is not functioning as well.”

Chang and her research team studied this in 29 people who had been infected with COVID about seven months earlier, nine of them hospitalized for their illness. Each patient had at least one ongoing neuropsychiatric symptom.

The study group was matched with a control group of 21 people with no known history of COVID infection.

In addition to the functional MRI scans, each participant performed tests to evaluate thinking and memory skills, emotional health, movement, pain, fatigue, depression and anxiety.

“It takes them so much more effort to do it. We are showing that the brain has to work harder in order to perform the task,” Chang said.

Patients in the study also had lower motor endurance, Chang said. They walked slower. Their dexterity was impacted. They also reported more anger, sadness and stress, while also feeling like they had less meaning and purpose.

These patients would benefit from both physical rehabilitation and psychiatric treatment, she noted.

Chang likened the brain changes to what happens in HIV patients and in those with traumatic brain injury.

No one knows how long the symptoms will last and when their brains might return to normal functioning, she said. It’s possible it will be very individual, with people recovering at different rates.

“COVID is not exactly the same as the other viral infections, other brain injury conditions,” Chang said. “But at the same time, it doesn’t matter what the cause is, the brain still has to, once it’s injured, compensate. It has to work harder. And that’s what we are seeing.”

The findings were published online April 26 in the journal Neurology.

Dr. Helen Lavretsky, director of the Long-COVID Psychiatry Clinic at UCLA, said the paper is helpful as it documents these patients’ experience. She was not involved in the study.

“They have to work harder than the controls in order to function at the same level,” Lavretsky said, noting the similarity to Alzheimer’s disease, mild cognitive impairment, traumatic brain injury and “chemo brain.”

The experts are just learning what it will take to help these patients improve, she said.

“The younger they are, the more likely they will improve. It will take months, many months,” Lavretsky said.

One of Lavretsky’s specialties is integrative medicine, so her recommendations for improvement include memory exercises, stress reduction and acupuncture to calm inflammation in the body.

“It’s becoming a chronic disease. It can get better with a lot of management for chronic disease,” she said.

Even mild infections can lead to long COVID, Lavretsky said. Having preexisting conditions, including attention deficit hyperactivity disorder, asthma, prior viral infections or autoimmune disorders increases the risk for long COVID.

Some of these treatments focused on well-being can be expensive and may not covered by insurance, which can increase disparities, she noted.

One study limitation is that it was mainly conducted in patients who had the Delta variant, and it’s not clear whether people who had other variants would have the same symptoms. Also, antibody testing was not done in the control group to confirm they never had COVID.

Researchers now plan to continue working with the study participants, doing repeat brain scans to gauge improvement over time, Chang said.

About 650 million people worldwide have had COVID infections, Chang said, with some estimates saying that 10% will experience long COVID.

“So, you’re talking about 65 million people worldwide who could have this condition,” Chang said. “That’s a lot people.”

The World Health Organization now estimates COVID infections at more than 764 million cases, with deaths at more than 6.9 million.

More information

The World Health Organization has more on post-COVID-19 condition, or long COVID.

SOURCES: Linda Chang, MD, professor, diagnostic radiology and nuclear medicine and neurology, University of Maryland School of Medicine, Baltimore; Helen Lavretsky, MD, director, Long-COVID Psychiatry Clinic, UCLA Health, Los Angeles; Neurology, April 26, 2023