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Scans and cognition tests collected from hundreds of people suggest coronavirus infection is associated with “a significant, deleterious” change in the brain, according to a study published Monday from scientists in the United Kingdom. 

The paper, published in the journal Nature, draws on data in the U.K. Biobank from 401 people between the ages of 51 and 81 who had COVID-19 through April 2021. 

Researchers analyzed data from brain scans and tests collected from participants both before they were infected with the disease, and from a second round conducted later, close to five months on average after they tested positive. 

That data was also compared to results from 384 similar people who had not had not gotten sick, as well as a handful of people who had pneumonia and influenza.

“To our knowledge, this is the first longitudinal imaging study of SARS-CoV-2 where participants were initially scanned before any had been infected,” the study’s authors wrote.

To measure the disease’s impact on people’s ability to complete cognitive tasks, the scientists looked at data from “trail-making” tests where people are timed on drawing lines between certain numbers or letters. Those who had tested positive for COVID-19 took “significantly greater time” to complete the tests, even after excluding people who had survived a case severe enough to be hospitalized.

Assessing the brain itself through a series of MRI scans, the researchers found evidence of an average decline in the overall size of the brain following COVID. The scans showed signs of tissue damage in areas of the brain related to smell, as well as a reduction in gray matter in parts linked to smell and memory. 

“This is concerning. And I think what it suggests is that the balance of the information that we’re accruing does indicate that COVID is a disease that could create persistent symptoms,” former FDA Commissioner Dr. Scott Gottlieb told “Face the Nation” last year, after results from the U.K. Biobank’s study were first released as a widely-shared preprint.

“This isn’t a benign disease. This is something you want to avoid,” added Gottlieb.

Studying “long COVID” in the brain

Researchers around the world have been ramping up efforts to study long-term symptoms from COVID-19 in the brain — part of an array of conditions dubbed “long COVID” or “post-acute sequelae of COVID-19” that can persist for many months after people appear to have recovered from the “acute” stage of their infection. 

Last year, one survey published by the Centers for Disease Control and Prevention found close to two-thirds of Americans who tested positive reported at least one long-term symptom more than four months after being infected — 55.5% included “cognitive dysfunction,” like difficulty concentrating or memory loss. 

Funded by a COVID-19 relief bill passed by Congress in 2020, the National Institutes of Health last year stood up a sweeping $1.15 billion effort to study long-term COVID-19 symptoms across the country called the RECOVER initiative. The federal effort spans a number of studies examining the causes and effects of long-term COVID-19 symptoms that officials hope might unlock the next clues to answering questions around the impact the infection has on the brain. 

“The question is, are you looking at basically changes in connections that are related to the fact that there was a loss of smell? That will look like one thing. Or are you looking at viral-induced injury? That will look like something different. So this study poses that question that needs to be answered,” said Dr. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke. 

Included in RECOVER is autopsy research, which examines the brains of people who suffered from long COVID after they die from other reasons, like cancer or a heart attack. 

“An MRI basically images water. So it doesn’t tell you what’s going on at the cell level or the connection level. But, you can get at that by looking at brain tissue under the microscope and using advanced techniques to study it,” said Koroshetz. 

Long-term issues might be linked to parts of the virus still lingering in the body, Koroshetz speculated, or the result of immune responses first triggered by the infection that are harming the body. Nailing down the causes will be key to helping scientists develop new treatments, beyond only testing medications intended to reduce people’s symptoms. 

“Hopefully, when we get more understanding of the biology, we can do trials to try to kind of normalize the body, get rid of the virus, treat the autoimmune reaction, reset the immune system. Those will hopefully get going within the year,” said Koroshetz.