Patient gets EEG test.Share on Pinterest
Bisual Studio/Stocksy United
  • A new study found that even mild coronavirus infection was associated with changes in the brain, especially in areas related to the sense of smell.
  • The new study included around 400 middle-aged and older adults who had a brain scan done before coronavirus infection as part of the UK Biobank.
  • Researchers found that people who had a coronavirus infection had greater loss of gray matter in the brain.

Coronavirus infection may cause a greater loss of gray matter and structural changes in certain parts of the brain than what occurs naturally due to aging and other factors, a large new study found.

Previous studies have looked at brain changes in people who had COVID-19. But the new study, which was published March 7 in the journal Nature, stands out because it involved brain scans on people before and after coronavirus infection.

“To our knowledge, this is the first longitudinal imaging study of SARS-CoV-2 [the coronavirus that causes COVID-19] where participants were initially scanned before any had been infected,” Lead author Gwenaëlle Douaud, PhD, wrote along with co-authors.

Researchers also included a group of people who hadn’t been infected with the coronavirus. This enabled researchers to look at the impact of infection from the effect of aging and other factors, including those that increase a person’s risk of severe COVID-19.

While the study highlights the impact that coronavirus infection can potentially have on the brain, experts cautioned that we don’t know whether these changes will have a long-term effect on people’s thinking, memory, or health.

The new study included around 400 middle-aged and older adults who had a brain scan done before coronavirus infection as part of the UK Biobank, a long-term health study of half a million UK participants.

These people had a second brain scan done after infection, the majority within 6 months of their diagnosis. Most of these people had mild to moderate symptoms, although 15 were hospitalized due to COVID-19.

“Despite the infection being mild for 96% of our participants, we saw a greater loss of grey matter volume, and greater tissue damage in the infected participants,” Douaud said in a statement. “They also showed greater decline in their mental abilities to perform complex tasks, and this mental worsening was partly related to these brain abnormalities. All these negative effects were more marked at older ages.”

Researchers also included a second group of 384 people who did not have a coronavirus infection. This group was similar to the first in terms of age, sex, ethnicity, and time between their two scans.

When comparing the brain changes that occurred over time for the two groups, researchers found that people who had a coronavirus infection had a greater loss of gray matter in the brain.

These changes were mainly in areas of the brain involved in the sense of smell. Another area that was affected is one that plays a role in the memory of events.

Brain scans also showed signs of brain-tissue damage in areas involved in the sense of smell.

In addition, there was an increase in cerebrospinal fluid and a decrease in the whole brain volume. These changes suggest a more widespread loss of gray matter, in addition to the loss directly related to areas involved in the sense of smell, the researchers wrote.

The structural changes in the brain were “modest in size,” they added. The average reductions ranged from 0.2 percent to 2 percent.

In comparison, in a part of the brain called the hippocampus, the typical age-related gray matter loss per year is around 0.2 percent in middle age and 0.3 percent in older age.

People who had a coronavirus infection also performed worse on a cognitive test that measures executive function and attention. The results were similar even when researchers excluded people who had been hospitalized.

This test, though, is not a comprehensive assessment of thinking abilities and memory.

The researchers emphasized that their results represent average changes, meaning not every person who gets a coronavirus infection will experience similar changes in the brain.

In addition, the study only included middle-aged and older adults, so the impact of the infection on the brain may be different in younger people.

The majority of people in the study were also white, so the findings may not apply to other groups.

The fact that many of the changes occurred in smell-related areas of the brain may be due to the loss of smell that occurred in many people with coronavirus infection, the researchers suggest.

The lack of sensory input to the smell-related areas of the brain — or inflammation in the smell-related structures of the nervous system — could explain the loss of gray matter and other changes, they write.

Loss of the sense of smell was a common symptom before the Omicron variant. This study was carried out before the emergence of this variant.

While the brain changes seen in this study warrant further investigation, it’s too soon to know how concerning they are.

There are also many questions that remain. Are there differences between people who are vaccinated versus those who are not? Does everyone who had a loss of smell have similar changes in their brain? And can the brain recover from these changes?

“Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up,” the researchers wrote.

A previous study found that olfactory training in people with a loss of smell — for a non-COVID reason — is associated with an increase in gray matter in parts of the brain involved in the sense of smell.

Coronavirus infection is not the only condition or factor that causes these kinds of changes in the brain.

One 2022 study that also used UK Biobank data found that air pollution was associated with a decrease in brain volume and an increase in white matter lesions. These types of lesions are linked to an increased risk of stroke and neurodegenerative disease.

Another 2021 study published in The Journals of Gerontology suggests that the Western lifestyle itself can lead to greater age-related decreases in brain volume, compared to those seen in indigenous people living a traditional lifestyle.

Alcohol consumption is another factor that can impact the brain. A recent study suggests that even moderate drinking is associated with reduced brain volume.

Like the recent COVID study, this one was large, involving more than 36,000 adults.

This allowed researchers to take into account other factors that might affect brain volume, like age, sex, body mass index, smoking status, socioeconomic status, and county of residence.

Even after controlling for these factors, “we still found an effect in 90 percent of the regions of the brain, including strong reductions in gray and white matter across the brain,” said Reagan R. Wetherill, PhD, a research assistant professor of psychiatry in the University of Pennsylvania Perelman School of Medicine and author of the 2021 study.

“To me, that was indicative of alcohol having a negative effect on the brain,” he added. “And it goes along with the pre-clinical literature looking at alcohol’s effects on the brain and body.”

As for the cause of the brain changes related to alcohol consumption, Wetherill said some research suggests it is related to oxidative stress that causes damage to brain cells.

Other research has found that inflammation may also play a role in alcohol-related brain damage. Oxidative stress and inflammation are interlinked and can influence how diseases progress, including COVID-19.

One study in hamsters suggests that inflammation in cells in the olfactory system may be responsible for the loss of smell seen with coronavirus infection. Other research suggests the same mechanisms might be involved in causing some of the symptoms of long COVID.

Wetherill said oxidative stress and inflammation are a common thread among many conditions.

“You’re seeing a lot of overlap in these kinds of exposures — to a virus or toxic substance or pollutant that the body is reacting to,” she said. “Chronic or severe exposure to these seems to have this negative effect on the body and the brain.”

Research on the effects of alcohol also suggests that the brain can recover from some of the damage caused by this kind of chronic exposure.

“When individuals who have alcohol use disorder go into treatment and have been abstaining for about 6 months, you can see neurogenesis,” she said. “They’re getting some of their brain volume back and their cognitive functions are improving.”

Additional long-term research on COVID-19 patients will be needed to see if there is a similar rebound in the health of the brain after the acute effects of infection have passed.

But the COVID-related brain changes seen in several studies have scientists concerned that the damage may contribute to Alzheimer’s disease or dementia later on in some people.

In response to this concern, the Alzheimer’s Association and representatives from more than 30 countries have joined together to study both the short- and long-term impacts of COVID-19 on the brain.