A colourful image of a brain in hues of purple, pinks and greens.
Photo: Fakurian Design/Unsplash

Brain fog (difficulty thinking or concentrating) and memory issues are just a few of the neurological symptoms that can linger for COVID-19 long-haulers.

Although research shows many COVID-19 survivors suffer cognitive impairments after being infected, there are currently no clinical guidelines that consider the neurological impacts of the virus.

Dalhousie University professor Carlos Hernandez-Castillo hopes his research examining cognitive abnormalities in COVID-19 survivors will help change that.

His research project is one of 15 recently awarded a Research Nova Scotia New Health Investigator Grant. The study will evaluate brain abnormalities in survivors by analyzing a large sample of data gathered from clinical assessments, cognitive scores, and brain magnetic resonance imaging (MRI).

“What I’m interested in studying are the cognitive deficits that result from the infection …We know that at least the patients who are hospitalized show a lot of different cognitive deficits, including deficit on attention and cognitive function, executive function, memory, verbal fluency,” Hernandez-Castillo said in an interview.

Dalhousie University professor and researcher Carlos Hernandez-Castillo. Photo: Contributed

“So, it’s a really broad constellation of symptoms. That actually makes it really difficult because some people perceive some symptoms and other people perceive something different. That’s why we need a really large amount of data to be able to group these people and find out what is happening in the brain.”

In addition to conducting research with his Nova Scotia team, Hernandez-Castillo is collaborating with researchers in London, Ont., Toronto, and Mexico City. He’s also hoping to secure partnerships in other jurisdictions to help aggregate the data and get a better idea of where the disease impacts the brain and how it leads to various cognitive deficits.

“Right now we have reports that say, ‘OK, we have people with this, with that and with that,’ but nobody has enough data yet,” he explained.

“We are working to get enough to say, ‘OK, the people that actually have attentional problems, they show similar lesions in this part of the brain, for example. And all the people that [have issues with] verbal fluency also have these kinds of lesions.”

Hernandez-Castillo said researchers have also found a link between the severity of a patient’s cognitive issues and the severity of their COVID-19 infection. Those who had milder infections tend to not be impacted as much as those who were hospitalized and required oxygen and ventilation.

“The number they have right now is that of the people that have a severe infection, at least 60% of them show neurological, psychological, and psychiatric symptoms,” he said. “In the mild patients, this number is reduced.”

He points to other studies suggesting the virus penetrates the brain via the olfactory bulb. Basically you breathe the virus in and it breaches the blood-brain barrier, resulting in more anatomical damage.

“So there is degeneration of the brain that is caused directly by the virus,” he said.

Last March, a Harvard Medical School article about the hidden long-term cognitive effects of COVID-19 noted the “inevitable conclusion” from several studies was that COVID infection frequently leads to brain damage, particularly in those over the age of 70.

“While sometimes the brain damage is obvious and leads to major cognitive impairment, more frequently the damage is mild, leading to difficulties with sustained attention,” the author noted.

13% to 15% will struggle with cognitive issues

Study participants will complete a battery of cognitive tests created by Hernandez-Castillo’s co-collaborator and Western University neuroscientist Adrian Owen. Via an online platform, participants will complete a series of tasks that help pin down their cognitive deficits.

Researchers will then compare those test results with a patient’s brain images to determine if and where abnormalities exist. The images will also be compared with data from healthy controls to give researchers a better idea of what’s happening in the brains of those who were infected with SARS-CoV-2.

“We take one group and we compare to the other and we see, ‘Oh, there is a difference in the volume [of grey matter — the outermost layer of the brain] in certain areas,’ and then we can use that to find an association with the symptoms that that group is exhibiting,” he said

“The same can be done for the white matter, [which are] the paths, the connections between neurons. We can also use different analytic techniques and find out if there is a break in these connection lines between neurons that also can lead to other kinds of deficits or impairments.”

Hernandez-Castillo said based on his own research, between 13% and 15% of people infected with COVID-19 will go on to struggle with cognitive issues.

“The percentage may not be big in terms of everybody who got COVID will have these things, but because there are so many cases, when you multiply that 15% it’s a huge number of patients that may need some kind of treatment,” he said.

Earlier this week, researchers at the University of California San Francisco published a study looking at patients who develop cognitive symptoms following a mild — didn’t require hospitalization — COVID-19 infection.

They discovered some have abnormalities in their cerebrospinal fluid similar to what’s found in people with other infectious diseases, and suggest an over-stimulated immune system may play a role.

Hernandez-Castillo said his study will give researchers a better understanding of the mechanisms through which the virus affect our brains. This will be instrumental in the development of targeted therapies and medications.

Hernandez-Castillo expects to begin recruiting participants for the study this spring, and to have preliminary data by as early as the end of this year. The study will be longitudinal, as he hopes to be able to follow patients over a two to three-year period to explore how their cognitive deficits might change, worsen, or improve over time.

“We want to do this every six months for two years at least, so we can see if the deficit gets worse or they get better, because now we have all the information about these long haulers, the people who recovered but are still having symptoms over time,” he said.

“Because we are interested in the long term, we don’t need patients in the acute stage. We’re going to study people that have already recovered and see how they’re doing after they come back to their regular life.”

In addition to Adrian Owen at Western University, Hernandez-Castillo’s study collaborators include Robert Bartha at the Robarts Research Institute in London, Ont., Simon Graham at Sunnybrook Health Centre in Toronto, and Juan Fernandez at Universidad Nacional Autónoma de México.

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Yvette d'Entremont

Yvette d’Entremont is a bilingual (English/French) journalist and editor, covering the COVID-19 pandemic and health issues. Twitter @ydentremont

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