World- First Discovery by Sydney Scientists Reveals the Hidden Cause of Organ Damage in COVID-19 and Other Deadly Conditions
Australian researchers have uncovered a previously unknown biological process where red blood cells, not traditional clots, are the hidden cause of organ damage in severe COVID-19, heart attack and stroke sufferers.
The discovery, published today in the prestigious journal Nature, opens the door to new treatments to restore healthy circulation for COVID-19 patients and improve outcomes for intensive care patients worldwide.
Published in Nature, the study reveals that under low oxygen conditions, such those experienced during COVID-19 or heart attacks, the inner lining of blood vessels begins to die through a process known as necroptosis. This triggers nearby red blood cells to rupture, releasing sticky remnants that clog up the smallest blood vessels and cut off oxygen to critical tissues. "We've discovered a completely new blood-clotting mechanism that has nothing to do with the traditional clotting system involving platelets or fibrin," said lead author Professor Shaun Jackson.
"Instead, dying cells cause red blood cells to burst and their membranes act like a biological glue - sealing off damaged blood vessels and blocking blood flow to vital organs." This previously unknown phenomenon, which the researchers call an "RBC Endo-seal," appears to be the body's emergency response when traditional clotting can't operate – such as in the low-oxygen, acidic environments seen in severely ill patients.
Implications for COVID-19, Stroke and Heart Attack Patients
COVID-19 can cause serious damage to small blood vessels, making it harder for blood to circulate properly. This damage, called microangiopathy, reduces capillary function by 60–90%, leading to complications in both acute infections and long COVID-19.
Initially, scientists thought excessive fibrin - a blood-clotting protein - was the main cause of blocked vessels. However, blood-thinning treatments have shown limited benefit.
This research - which included examination of autopsy tissues of COVID-19 patients in New York - found widespread blood vessel (endothelial cell) injury, swelling, and capillary congestion. It shifts our understanding of COVID-19's vascular effects from simple clot formation to a more complex process involving red blood cell destruction.
This new form of microvascular blockage was not only widespread in COVID-19 patients, but it was also found in people who died from heart attacks, gut ischemia and strokes. In mouse models, blocking the key necroptosis pathway dramatically reduced both red cell damage and downstream organ injury.
"This mechanism helps explain why many patients with severe COVID or other critical illnesses suffer from multiple organ failure, even when clotting is under control," said Professor Jackson. "It's a whole new chapter in vascular biology."
The implications are profound. By targeting this process, scientists may develop new treatments to restore healthy circulation for COVID-19 patients who are experiencing persistent vascular complications. It could also shift how ICU patients are treated around the world.
"Rather than targeting platelets or clots, therapies might instead aim to prevent endothelial cell death or block the red blood cell damage that follows," Professor Jackson said. "By stopping this process early, we may be able to preserve blood flow, protect organs and ultimately save lives."
Research Highlights
The research was led by Professor Shaun Jackson at Thrombio Sydney in collaboration with 20 leading scientists from research institutes including the University of Sydney, University of Queensland and New York University.
Studies were conducted across human COVID-19 autopsy tissues, advanced live imaging of blood vessels and animal models of ischemia reperfusion injury.
"This is a groundbreaking moment in medical science," said Professor [xx], a co-author from the [xxx]. "It rewrites what we thought we knew about the processes of bleeding and clotting." Pending appropriate funding and support, Professor Jackson's team will now turn its attention to identifying new therapies to target red blood cell damage, potentially revolutionising care for long COVID and intensive care patients everywhere.
Key Facts:
Main Discovery:
In life-threatening conditions such as COVID-19, heart attacks and strokes, the inner lining of blood vessels dies via a via a process called necroptosis.
This triggers red blood cells to rupture, leaving behind sticky membrane fragments that clog small blood vessels.
These fragments form a new type of vascular sealant that prevent bleeding but cause oxygen starvation in tissues, leading to organ damage.
Why It Matters?
This newly identified process explains why many COVID-19 patients and those with ischemic injuries, including heart attack and stroke, suffer from multiple organ failure – even when treated with blood thinning medication.
It challenges long-held beliefs that platelets and fibrin are the primary drivers of microvascular obstruction.
It provides a new target for therapies for by targeting the red blood cell response instead traditional clotting.
Potential Impact:
New treatment strategies could restore healthy circulation for long COVID-19 patients.
Better outcomes for intensive care patients, where existing blood thinners have failed to prevent micro-vascular damage.
