Even a mild case of COVID can cause brain changes. It's too soon to know if the damage lasts.

A new study provides the most conclusive evidence yet that COVID-19 can damage the brain, even in people who weren't severely ill.

The study, published Monday in "Nature," used before-and-after brain images of 785 British people, ages 51 to 81, to look for any changes. About half the participants contracted COVID-19 between the scans – mostly when the alpha variant was circulating – which left many people at least temporarily without a sense of smell.

Analysis of the "before" and "after" images from the UK Biobank showed that people infected with COVID-19 had a greater reduction in their brain volumes overall and performed worse on cognitive tests than those who had not been infected.

The 15 participants who were sick enough with COVID-19 to require hospitalization showed the most brain changes, but even those who had much milder disease showed differences, the study found. The oldest participants had more changes on average than younger ones.

The brain areas most affected were those that are related to smell, which makes sense, since many of the people infected around the world lost their sense of smell, said Gwenaëlle Douaud, who led the research.

It has been known that people who lose their smell for prolonged periods also lose volume in brain areas related to smell. "Lose it or use it," said Douaud, a neuroscientist at Oxford University.

If smell recovers, usually the brain region does, too, she said.

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Loss of smell is also one of the earliest signs of impending illness with diseases like Parkinson's and Alzheimer's, said Dr. Ronald Petersen, who directs the Mayo Clinic Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging. The olfactory structure involved in smell "lives next door" to a memory structure in the brain, he said.

The cause of these changes hasn't been determined, but it may partly be the result smell loss, Douaud said, or of the virus entering the brain or causing an inflammatory or immune response that indirectly changes the brain.

It's possible, she said, that the omicron variant, which seems to have less impact on sense of smell, will have triggered fewer brain changes than earlier variants, but it's too soon to know.

Douaud said that because brain changes appeared to increase with age in her group, she thinks younger people will likely have less damage, if any.

But Dr. George Vavougios, a neuroscientist at the University of Cyprus, said it's too early to know for certain. Many people who complained of smell loss or distortions after infection were younger or previously healthy.

And in his out-patient clinic, he sees no difference in brain fog complaints among people who contracted the alpha, beta or delta variants. Between 40% and 50% of those with each variant have noticed cognitive impairments since their infection.

Petersen said he was struck by the fact that even people with milder cases of COVID-19 showed these brain changes, though he was surprised that the changes would be dramatic enough over just five or six months to be detectable on brain scans.

The study spurred him to want to look at brain scans he has from his own research into aging to see if he can detect similar changes. "Larger studies could shed light on this," he said.

It's unclear whether these changes will reverse with time. Douaud hopes to be able to rescan the same people in a year or two to learn about long-term effects.

In a year or two, their brains "may have entirely normalized." But still, she said, "better not to catch (COVID-19), if possible, and better to be vaccinated."

It will be crucial, Vavougios said, for primary care doctors and specialists to follow their patients who had smell issues from COVID-19 and validate any complaints of brain fog.

'LIFE-ALTERING': As millions cope with smell loss from COVID-19, researchers find new explanations and possible treatments

There are things people can do to boost their brain's resilience after a hit like COVID-19, said Patrizia Vannini, a neurologist at Brigham and Women's Hospital in Boston, who studies the infection's affect on the brain.

"Although certain factors might make some people more resilient than other, resilience has been shown to involve behaviors, thoughts and actions which everyone can learn and develop," she said in an email.

Those include forming or maintaining social connections, adopting a healthy lifestyle including good nutrition, sleep and exercise; seeking help when needed or if you feel stuck; and embracing "healthy thoughts by keeping things in perspective," she said.

In a recent study, Vannini and her colleagues showed that older people had greater resilience during the pandemic when they used approaches like humor to cope. Those who fared worse gave up trying to deal with the situation.

"To build up your resilience it is important to not only enhance certain behaviors," she said, "but also reduce or avoid other behaviors."

Contact Karen Weintraub at [email protected].

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

This article originally appeared on USA TODAY: Even mild COVID can cause brain damage, for how long isn't known

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