Organ failure from Covid, stroke, heart attack linked to red blood cell damage
Red blood cells damaged by long Covid and clogging blood vessels have been found to cause organ failure, providing a hard-fought missing link in cardiac science.
Researchers have discovered a breakthrough link between organ failure and long Covid after overcoming contentious Covid-era autopsy regulations and one of the medical profession’s most high-profile legal disputes.
A seven-year Australian study with implications for strokes and heart attacks has “imagined the unimaginable” in discovering how coagulated red blood cells can clog blood vessels in the same manner as traditional blood clots, laying the groundwork for future treatment.
The research, published in Nature on Thursday, gives the first clear indication of how severe Covid cases can shut down organs despite patients maintaining otherwise healthy arteries.
Lead researcher Shaun Jackson, the founder of stroke drug research group ThromBio, found red blood cells would burst and form thick membranes under low oxygen conditions, blocking microvessels in the process and cutting off blood flow.
Strokes, Covid and heart attacks all create these low-oxygen conditions by rupturing the lining of blood vessels, with Covid reducing capillary function by 60 to 90 per cent.
With an eye to these newly discovered microvascular processes, researchers can better develop treatments distinct from anticoagulants that prevent red blood cell build-up.
“A good body of research asks more questions than it answers, and it opens the door for new ways of thinking and potentially new therapies. That’s how we see this,” Professor Jackson said.
“In the case of Covid, it’s ironic that a disease that’s so new is opening up opportunities in lots of other areas of medicine.
“Now that we’ve pinpointed the key mechanisms that cause this red cell damage … there are some drugs we can use to mop up the toxic things that are released. There’s a very broad range of human diseases where this process could be very important.
“Maybe that is explaining a lot of the mystery around – whether it was your brain, or your kidney, or your liver, or your heart – why they were failing.”
Professor Jackson is also the developer of the stroke drug TBO-309, which had its human trials delayed after he was dumped by the Heart Research Institute in a case of alleged whistleblower retribution that ultimately was dismissed by the Federal Court.
The latest research marks a partial vindication for Professor Jackson as it solidifies the underlying science of TBO-309. Professor Jackson hoped the study results would return momentum to the drug’s clinical progress.
“When one door closes, other opportunities present, and it’s allowed us to focus on getting these studies out in the public domain, as well as trying to progress the clinical trials,” he said.
“Our priority is getting these innovative new treatments to patients with stroke and other diseases (and) the process around the management of the trial has been frustrating. I’d be the first to acknowledge that.”
While study research began in 2018, it changed course during the pandemic after autopsies showed patients suffered unexplained microvascular damage.
American pathologist Amy Rapkiewicz discovered the damage after fiercely petitioning New York health authorities to let her inspect cadavers early in the pandemic. “When the first Covid outbreak came in Australia, we wanted to get access to autopsy specimens, but it was just about impossible,” Professor Jackson said.
“A lot of the pathology labs and facilities weren’t set up for these sorts of viruses, so we were very reliant on what was going on in Italy, China and the US, which had the early surges.”
Professor Rapkiewicz said it was validating to see her autopsy work had proved useful years down the line. “Very early on in the pandemic, myself and my other autopsy colleagues knew autopsies needed to be performed,” she said. “The challenge was educating the administration on how those autopsies could be performed safely.
“After they agreed, I was aggressive about pursuing cases that were untreated. I wanted to capture what was happening at the earliest points. At the same time, people who know how passionate I was about autopsy were calling and texting asking what we were finding to explain what they were seeing in critical care patients.
“It was challenging in the sense of trying to co-ordinate these cases and get the information out as fast as I could to see if it would be helpful for treatment. After I did the first 10 or so cases, I summarised my findings and would speak to anyone who listened.”
Victor Chang Cardiac Research Institute founder Bob Graham said the applications for the research could likely extend to the treatment of sickle cell disease and surgical blood flow deprivation known as reperfusion.
“This is a beautiful paper,” he said. “(It) is research that allows you to imagine for the first time the unimaginable. Until you knew there was this pathway you can’t start looking for it.
“Now that we know that it’s there due to this beautiful piece of work from Shaun’s lab, everyone’s going to start looking at it in lots of other conditions.”
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