Canadian researchers find brain inflammation in patients with long COVID

Leslie Ann Coles knew "almost immediately" something was wrong after her COVID-19 infection in January 2021.

The filmmaker from Woodbridge, Ont., had never had writer's block in her life -- but she couldn't find the words to make revisions to a screenplay she'd been working on.

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"It was really, really frightening," Coles said.

Her emotional state changed too.

"I've never in my life suffered from depression," Coles said. "My friends refer to me as the eternal optimist."

But her usual passion for life and work had waned, leaving her feeling "apathetic, for lack of a better word," she said.

Researchers have been trying to understand what causes the many symptoms of long COVID, including neurological issues suffered by an estimated hundreds of thousands of Canadians like Coles.

Now, a team led by the Centre for Addiction and Mental Health (CAMH) has found physiological evidence of brain inflammation in people with cognitive and depressive symptoms months after their COVID-19 infections.

Autopsies of people who died in the midst of severe COVID-19 infection have previously shown they had brain inflammation, said Dr. Jeffrey Meyer, head of the neuroimaging program in mood and anxiety at CAMH and senior author of the study published Thursday in JAMA Psychiatry.

The current study shows brain inflammation inpeople who have recovered from acute COVID-19 but go on to have lasting neurological problems -- even though their initial infection wasn't severe, he said.

"These are people who've got long COVID and have actually not been hospitalized. They have mild to moderate severity acute COVID, but then have considerable symptoms thereafter," Meyer said.

"Our study shows that there's inflammation months to over a year later in people who've got long COVID."

The researchers did positron emission tomography (PET) scans on the brains of 20 participantswho had started suffering from depression within three months of testing positive for COVID-19.

Most of them had additional cognitive issues associated with long COVID, including problems with memory and concentration, also known as "brain fog."

The researchers compared those scans to 20 brain scans from "healthy" people that had been done prior to the pandemic.

They found that people who had long COVID had higher levels of translocator protein, or TPSO, in their brains. TSPO appears on glial cells, which increase with inflammation.

The most pronounced increase in inflammation was in two areas of the brain -- the ventral striatum and dorsal putamen, the study said.

Those are parts of the brain associated with the ability to experience enjoyment, energy and motivation levels, cognitive processing and speed of movement.

"We know that when there's injury to these brain regions you get some of the symptoms that we're seeing in the people with long COVID," Meyer said.

Long COVID sufferers have been eagerly awaiting these findings "for validation that brain fog is real and caused by functional changes from COVID-19," said Susie Goulding, founder of the COVID Long-Haulers Canada online support group, which helped recruit study participants.

"This concrete evidence will hopefully bring understanding and guidance" to family doctors who encounter patients describing neurological symptoms after COVID infection, Goulding said in a text message to The Canadian Press.

Dr. Angela Cheung, co-lead of a national long COVID research network and senior physician-scientist at the University Health Network in Toronto, said the study confirms what long COVID researchers have suspected for some time.

"We have always thought that inflammation plays a part," said Cheung, who was not involved in the CAMH study.

"It's been difficult to measure inflammation in patients." she said. "This study shows that in people with persistent depressive and cognitive issues, that there is neural inflammation in the brain."

But Dr. Lakshmi Yatham, a psychiatrist at the University of British Columbia who researches mental health issues related to COVID-19, said that although the study is valuable, there are important limitations to consider.

"It's a good first attempt to look at the inflammation. But you cannot at this stage attribute that the inflammation is what's responsible for depressive symptoms," Yatham said.

One limitation, he said, is that some of the participants had previous experiences with depression.

However, Meyer said those people made up fewer than half of the participants, and any past depressive symptoms had resolved before they got COVID-19.

Yatham said further study is needed using a control group of people who have recovered from COVID-19 and didn't have long COVID to compare the levels of brain inflammation. That wasn't possible in the CAMH study because the brain scans of the control group had been done prior to the pandemic.

One of the next steps for the CAMH team is to "test out whether some kinds of anti-inflammatory or inflammatory-altering medications might be helpful for long COVID," said Meyer.

Cheung said other researchers are also planning anti-inflammatory medication studies.

Leslie Ann Coles has learned tactics to work around memory problems that persist to this day, including constantly writing things down and taking photos on her phone.

For her, like so many other long COVID sufferers, the next steps in research can't come soon enough.

"I hope they find ways in which this study helps people with long COVID recover," she said.

This report by The Canadian Press was first published June 1, 2023

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