AUSTIN (KXAN) — Scientists are working to understand the long-term effects of COVID-19, including on those who didn’t have serious infections. Research, including at the University of Texas at Austin, focuses on the effect of the coronavirus on the central nervous system and why some patients have lingering symptoms.

In the United Kingdom, researchers are studying the long-term effects of mild-to-moderate cases of COVID-19. One study led by the Wellcome Center for Integrative Neuroimaging at the University of Oxford examined how infection affects brain structure. 

Researchers performed brain scans and cognitive tests on 785 U.K. Biobank participants, 401 of which had been infected with COVID-19 between their first and second scans. UK Biobank is a biomedical database that collects information from U.K. participants. It contains data from half a million participants which can be accessed by approved researchers or scientists. 

“I think one of the really important aspects of this study is that it was the first longitudinal imaging study of patients who were imaged with brain MRIs before and after getting infected with COVID,” said Dr. Esther Melamed, director of research at the Post-COVID Clinic at Dell Medical School. “That really allowed the researchers to be able to compare what happened to the different brain regions before and after COVID.”

Dr. Anderson Winkler, a senior associate scientist at the National Institute of Mental Health, was one of the researchers in the study, which was published in “Nature.” In examining the brain scans, researchers found the infected participants had a greater loss in gray matter volume in the cerebral cortex of the brain, which is the outermost sheet of neural tissue. Gray matter is significant in processing information as it sends signals to the brain.

“We saw cortical thinning in areas associated with the sense of smell,” Winkler said. “We noticed a blurring of the contrast between the gray and white matter and we also saw changes in the diffusion of water molecules.”

The red-yellow coloring in the scan below shows areas of the brain that shrank the most from COVID-19 infection. These regions are related to where the brain processes smell, Winkler said.

The red-yellow regions shrank the most from COVID-19 infection. This scan shows the brain in the left hemisphere with inferior, side and medial views. (Courtesy ‘SARS-CoV-2 is associated with changes in brain structure in UK Biobank’)

Winkler said the reduction of gray matter was “more pronounced” in the group that had COVID-19 compared with the group that didn’t.

“These changes are an indication of tissue damage at the microstructure level and also a global reduction of brain size,” Winkler said.

Trail making test

Winkler said researchers also gave participants another test to measure the long-term effects of mild COVID-19 infections. The participants were given a sheet with dots that were numbered and were asked to connect the dots as quickly as possible.

“In terms of cognition, we also noticed that in one of the tests that they performed, the group that had COVID, it took a little bit longer to perform those tests,” Winkler said.  

Dr. Melamed and her team

Meanwhile, a team of collaborating researchers at UT Austin led by Melamed are looking into the neurological consequences of COVID-19 and why some individuals experience long-term COVID-19 symptoms.  

“(The American Medical Association) estimated 10 to 30% of COVID-19 survivors who may continue to experience different types of symptoms post-COVID,” Melamed said. 

These long-term symptoms are also referred to as post-acute sequelae of COVID-19 (PASC) infection.

“There are now several studies that have confirmed that patients, even those who are not hospitalized, who had mild disease, continue to experience different types of symptoms,” Melamed said. She added the most common tend to be “neurological in nature,” including brain fog, where an individual has difficulty with memory, attention and concentration.

“People are also experiencing headaches, visual changes, problems with swallowing, problems with pain in the mouth, changes in taste and smell that may be persistent, changes in hearing or hearing noises that it didn’t used to be there,” Melamed said.

There is a wide range of long-term symptoms individuals have identified after getting infected with COVID-19. UT Health Austin created a Post-COVID-19 Program in the summer of 2021 to better understand them, giving patients an opportunity to participate in research studies.

Additionally, the clinic provides education to community physicians through seminars and case presentations.

“There are different aspects of the clinic, including the clinical care of patients. There are educational programs that are part of the Post-COVID Program, as well as research,” Melamed said. 

The Health Transformation Building is home to the UT Health Austin clinic. (KXAN Photo/Maggy Wolanske)
The Health Transformation Building is home to the UT Health Austin clinic. (KXAN Photo/Maggy Wolanske)

Long-form COVID-19 symptoms and the impact on patients’ immune systems 

In the Health Discovery Building, Melamed and her team conduct immunological research that looks closely at patients’ cells and their communication proteins. The group uses patient blood samples to study the consequences of COVID-19 on patients’ immune systems. 

The first-step procedures are done before specific immune research happens.

One procedure utilizes blood samples to see if a patient’s immune system may be altered and cause the development of long-form COVID-19 symptoms.

Another procedure is a cell count of immune cells. In cases where patients have COVID-19 infection, their number of white blood cells will be higher. Counting the cells distinguishes those who had COVID-19 infection.

Art program 

One member of Melamed’s research team, Sam Bazzi, enjoys art as a hobby and previously participated in chalk festivals. When the pandemic hit, he used art as a way to spend his free time and as a coping mechanism to handle pandemic nerves.  

Bazzi then introduced the idea of an art program to Melamed.

“We thought it would be a really wonderful way to help people that were dealing with long COVID,” Bazzi said.

Bazzi created an eight-part series of classes on introductory drawing. The program is offered for free. Participants bring their own supplies such as pens, pencils, paper and rulers.

Each week, the program introduces a new technique like drawing a subject, implementing shading or setting up a still life.

“Being able to have kind of creative control over their art can be a very therapeutic way of dealing with this illness,” he said. 

He also saw the benefits of participants adding art into their lives as a way to slow down from daily tasks and refine their creative skills.

Bazzi said the art program brings together a sense of community and space for these individuals to connect with one another over similar symptoms. 

“So long-term COVID has a tendency to alienate people, because a lot is not known about it yet. And there’s a lot of information that we just don’t have yet. So, building a sense of community was really important for them,” Bazzi said.

Several members of the art program agreed to feature their art.

Looking to the future 

Melamed and her research team are hoping to conduct further research on what exactly impacts these patients after infection. 

“What we’re trying to understand is not only how the immune system is changing, but how other environmental, genetic and hormonal states may be influencing patients developing persistent symptoms of brain fog and other neurological complications,” Melamed said.