So far little work has been done on COVID-19’s potential impact on the brain. People were too focused on saving lives.

Normally, Adrian Owen would be inside an ICU these days, trying to read the minds of people with severely injured brains. Because of COVID-19, “I can’t do that right now. I haven’t been able to do that for three or four months. I have a whole team of people sitting in my lab, unable to directly assess patients,” said the renowned Western University neuroscientist who has devoted much of his career searching for signs of consciousness and awareness in unresponsive patients.

But then the crisis started escalating; reports starting to come in of people suffering neurological consequences, and it became apparent to Owen about six or eight weeks ago “that if we’re ever going to understand this, this is something we need to do, now.”

What he’s doing now is launching a massive study to explore the impacts of COVID-19 on the brain.

The online COVID-19 Brain Study aims to recruit 50,000 people with a confirmed, positive diagnosis of the virus. Using questionnaires and pop down menus, Owen and his collaborators will collect information, “completely anonymized and secure,” asking participants about their medical history, any underlying heart, lung or other health issues, the extent of their COVID-19 diagnosis and what happened to them.

They’ll be asked to perform cognitive games that assess memory, decision-making, planning and problem solving, and results will be compared against a huge database of millions of tests completed by a healthy, normal population.

No one leaves the ICU in good shape, cognitively,

For the study, Owen has partnered with Sunnybrook Hospital stroke neurologist Dr. Rick Swartz. They’re hoping for a large and diverse group (the study is available in English, French and Spanish). They hope that with 50,000 people they’ll have enough statistical power to tease apart “all of these little nuances,” Owen said, and answer questions like, are there certain proportions of the population that are more vulnerable to developing cognitive deficits — fuzzy thinking, brain fog, problems concentrating? Are there differences between men and women? Older people and young? Is it only people who were placed on ventilators? Is this something happening to everybody?

Timing is critical, said Owen, a professor in Western’s Brain and Mind Institute. “We can’t wait a year from now when potentially we’ll have eight million or more people who have survived COVID-19.” His hypothesis? “We’re going to see many, many people with profound cognitive impairment a year from now.”

“We have enough experience that we know that this is going to produce cognitive deficits,” and there are several possible reasons why, he said, including from the virus itself, the secondary effects on the respiratory system that might affect the flow of oxygen to the brain, to staying in ICU.

“Many different things are likely to contribute to the cognitive profile of people coming out of this.”

So far little work has been done on COVID-19’s potential impact on the brain. People were too focused on saving lives.

However, a recent review article raised the question of whether SARS-CoV-2, the pandemic virus that has killed nearly half a million globally and sent millions of other lives into free fall, is neurotropic, meaning toxic to brain tissue and to what extent it’s capable of damaging the central nervous system.

In a handout photo of Western University neuroscientist Adrian Owen, who, in collaboration with Dr. Rick Swartz, a stroke neurologist from Sunnybrook Health Sciences Centre and the University of Toronto, has launched a study to look at the possible effects of COVID-19 on the brain. Handout

During the SARS pandemic of 2002-03, many survivors suffered long-term neurological complications. The new virus shares many of the same features as its more lethal predecessor. Both use spike proteins to bind to a protein called ACE2 on the surface of “host,” in this case human host, cells, and some scientists have found ACE2 receptors scattered through the brain, on neurons as well as the star-shaped glial cells that help nourish them.

The virus might also invade the brain by several routes, the review article found, including  via the olfactory nerve, which might explain why people with COVID-19 so frequently report loss of taste and smell.

Other common neurologic complaints in COVID-19 include headache, stroke, impaired consciousness, seizure and encephalopathy.

This virus is new; there’s no long-term data on people who have recovered from COVID-19. “But there are plenty of reports of people reporting what in a clinical context we refer to as delirium,” Owen said. “There are people coming out of the ICU recovering from COVID and saying they don’t feel themselves. They’ve got fuzzy thinking. They can’t really concentrate. And this is sort of the typical profile that we know goes on to produce long-term consequences.”

High doses of some sedatives in the ICU can contribute to delirium, a kind of brain dysfunction that can lead to a serious state of confusion and even paranoid delusions that the brain lays down as “real” memories. Early evidence suggests that one-third of COVID-19 patients of all ages, and two-thirds of those with severe disease, show signs of delirium, according to Harvard Medical School researchers.

“I do most of my work with ICU clinicians, and they’ll often tell you, no one leaves the ICU in good shape, cognitively,” Owen said.

“The priority, and this is not specific to COVID, the priority in most ICU’s around the world is to get the patient out the door alive. They’re not trying to get them out making sure they’re cognitively intact and they have no memory impairments. People are typically fighting a battle between life and death. Cognitive deficits might not be a high priority at that point.”

People who spend time on ventilators generally experience cognitive deficits, the result of uneven delivery of oxygen to the brain, he said.

The pandemic virus can also cause blood clots that can lead to strokes.

The hope is to use the study’s data to design therapeutic strategies, “to work out what we need to do to deal with this,” Owen said. “You don’t want to put all your eggs into giving people memory training if it’s not fundamentally a memory problem that people have.

“It’s important we understand exactly what the problems are: Is this something that affects people’s memory? Their concentration? Their ability to make high-level decisions?”

It’s also important to get a better handle on the magnitude of the problem. “Is this something that’s going to affect 10 million in a year’s time, in which case that is a massive social and economic problem,” Owen said. “Or is this something that’s going to affect 20,000 people a year from now, in which case it’s something much more manageable.”

“You cannot tackle any problem to do with the brain unless you fully understand it.”

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