Saskatoon harbours one of the brightest lights on Earth. And, as a scientist in the midst of a global health crisis, Jake Pushie was drawn toward it.
When the pandemic hit, Pushie was at the Saskatchewan Cerebrovascular Centre where he was studying the effects of strokes. As troubling signs began to emerge that for some, COVID-19 may cast a shadow of ailments long after recovery, he shifted focus and looked to the synchrotron to explore the reasons why.
The Canadian Light Source is Canada’s only synchrotron — a particle accelerator that generates light millions of times brighter than the sun. This light from across the spectrum can be directed to illuminate all kinds of materials in their full atomic depth.
For Pushie, it offers an essential vantage point to explore the molecular wake that COVID-19 can leave on the vascular system, potentially elevating risks of chronic illness long into the future.
“(The synchrotron) lets us go all the way from the atomic to the anatomic level,” Pushie told Global News.
“We can zoom right in and look at individual cells and what’s changing with those cells. And then we can zoom out and look at that effect on the whole organ and then the organism level.”
His hypothesis is that for a significant number of people, severe infection may result in lasting damage to the body’s blood vessels. That damage can impair the circulation of oxygen, especially in highly vascularized organs like the heart, lungs and brain.
Over the long term, this could increase risk factors for conditions like dementia, stroke and heart disease.
The study is focused on the endothelium — the inner lining of blood vessels that spans the entirety of the circulatory system. Much like the lining of the lungs, these tissues are particularly vulnerable to COVID-19 infection and inflammation.
The endothelium is the crucial interface between the blood and the body’s tissues, and any enduring damage could reduce the ability of the vascular system to effectively oxygenate the body.
It was the persistence of certain symptoms among so-called COVID-19 long-haulers that first drew Pushie down this road. It struck him that frequently reported symptoms like brain fog, chest pains, kidney problems, all involve organs with heavy blood circulation.
“If you have a problem with the blood supply, the place you’re going to see that first will be the organs most highly vascularized and that most critically rely on consistent blood supply for their function. And that’s, I think, what we’re seeing in a number of these COVID cases after recovery.”
Recently, two studies have reported erectile dysfunction in men who have recovered from COVID-19, a development that doesn’t surprise Pushie.
“It’s a highly vascularized organ. And to get and maintain an erection, that’s a blood flow problem,” he said.
“You need those blood vessels to open up to supply enough blood to that organ to get an erection. So absolutely, any reduction in blood flow is going to cause a problem. But I think we also have to be cognizant that there are multiple factors here.”
COVID and Scar Tissue
The key question is the extent to which scar tissue could form along the endothelium in blood vessels after a COVID-19 infection. Like scars that develop on the surface of the skin — tissue that’s repaired, but never quite the same because it can’t sweat or grow hair — vascular scar tissue lacks the resilience and functionality of the healthy tissue it replaces.
“With blood vessels, … you need oxygen to diffuse out of those very thin-walled capillaries down at the ends where they deliver their oxygen for target organs to function,” Pushie said.
“If you’ve got swelling and inflammation, followed by remodelling around the blood vessels, those blood vessels … are not going to be able to deliver oxygen and other nutrients or remove waste from target organs as effectively.”
For some people, Pushie thinks this could produce a legacy of health conditions long into the future. He points to well-established links between vascular health and conditions like Alzheimer’s, heart disease and stroke.
The organic tissues under study are all from animals – mostly hamsters and ferrets. Human tissue for this kind of research is hard to come by, and the long-term nature of the study requires a focus on those who’ve recovered from the disease, largely ruling out post-mortem samples from those who’ve succumbed to it.
“We primarily focus on animals, simply because it’s very difficult to get human tissue at the moment in lots of countries, not just Canada. Certainly if we’re interested in looking at heart or brain, we’re only going to get that kind of tissue from patients who have died of COVID, which means we’re already biasing all of our research to the most severe cases. ”
By contrast, animal subjects are easily managed within the parameters of the research.
“In the case of animals, we can very carefully control conditions. We know exactly how long they were infectious for. We know how long it took for them to recover. And then we can monitor their behaviour after they’ve recovered and keep them for however long we need for the study. ”
The Brightest Light in Canada
The synchrotron is a powerful and essential tool in carrying out this kind of research, according to Pushie.
“Without the synchrotron, we simply wouldn’t be able to do the majority of our investigations,” he says. “And what that allows us to do is… drill down to the molecular level, which you just simply can’t do with what we call a laboratory source, an instrument that would sit on a bench in in a research lab. ”
Unlike a traditional microscope, the synchrotron shines light from across the spectrum — infrared, X-ray, microwave — all of which can illuminate subject materials in unique ways.
To achieve this, the facility accelerates bursts of electrons around a track, roughly the size of a football field, at rates verging on the speed of light. Vast amounts of energy are generated and channeled into highly-focused beams of light. That light is then directed into objects of all kinds: ancient coins, dinosaur bones, and now COVID-infected tissues.
‘Forewarned is Forearmed’
For all the unknowns that accompany the novel coronavirus, Pushie says it is all the more important to investigate and evaluate future risks for those who’ve recovered from infection.
“Even in the cases where people have recovered and they go back to their daily lives, they could be harbouring significant risk factors that they take with them into their future. I think of the old saying, ‘forewarned is forearmed’. It’s really important for people to understand that so they can make the most informed decision for themselves that they can.”
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