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Whether it’s a strange rash on a toe or a blood clot in the brain, the widespread destruction of COVID-19 has increasingly led researchers to focus on how the new coronavirus destroys the body’s blood vessels. .
As scientists have come to recognize this disease better, they have homed now on the vascular system – the body’s network of arteries, veins and capillaries, spanning more than 60,000 miles – to understand the disease above. This wide range and to find treatments can thwart its worst effects.
Some of the earliest insights into how COVID-19 might act as a vascular disease comes from studying the consequences of the most serious infections. Those revealed that viruses warp an important part of our vascular infrastructure: the simple layer of cells that line each blood vessel, called an endothelium or simply endothelium.
Dr. William Li, a vascular biologist, compares this lining to a new ice rink paved before a hockey match on which players and players glide along.
“When the virus damages the inside of the blood vessels and shatters the lining, it’s like ice after “You have an unresolvable situation with the blood stream,” said Li, a researcher and founder of the Angiogenesis Foundation.
In a study published this summer, Li and a team of international researchers compared the lung tissues of people who died from COVID-19 with those who died from the flu.
They found a stark difference: The lung tissue of COVID-19 patients had nine times more microscopic blood clots (“microthrombi ”) than the lung tissue of patients with influenza and coronavirus-infected lungs. also exhibits “severe endothelial damage”.
“The amazing thing is that this respiratory virus provides pathways for the cells lining the blood vessels, filling them up like a gum press and chopping the cells inside out,” Li said. “We found that the blood vessels become blocked and clot formed due to the damaged mucosa.”
It is known that coronavirus gets into cells by way of a specific receptor, called ACE2, found throughout the body. But scientists are still trying to figure out how the virus causes a series of events that cause so much damage to the blood vessels. One theory is that the virus attacks endothelial cells, Li said. Laboratory experiments have shown that the coronavirus can infect engineered human endothelial cells in lung tissue and other organs.
It’s also possible that the problems start elsewhere and endothelial cells suffer collateral damage as the immune system reacts – and sometimes overreacts – to the invading virus.
Endothelial cells have a series of important jobs; these include preventing blood clots, controlling blood pressure, regulating oxidative stress, and combating pathogens. And Li says that discovering how the virus endangers the endothelium may link many of the complications of COVID-19: “Effects in the brain, blood clots in the lungs and elsewhere in the feet and toes. COVID leg, problems with the kidneys and even the heart. “
In Spain, skin biopsy of special red lesions on the toes, called chilblains, found viral particles in the endothelial cells, leading the authors to conclude that “viral endothelial damage Cause can be the main mechanism. ”
Can the lining of our blood vessels be a common denominator?
With a surface area greater than a football field, the endothelium helps maintain a delicate balance in the blood. These cells are essentially “gatekeepers” for the bloodstream.
“The endothelium has developed a remote early warning system to alert the body to an invasion if something goes wrong,” said Peter Libby, research scientist and cardiologist at Harvard Medical School.
When that happens, endothelial cells change the way they work, he said. But that process can also go too far.
“It is the functions that help us stay healthy and fight invaders, when they get out of control, that it can actually make the disease worse,” says Libby.
In that case, endothelial cells fight their host and begin promoting blood clotting and high blood pressure.
“In patients with COVID-19, we have both of these markers of dysfunction,” said Gaetano Santulli, researcher and cardiologist at Albert Einstein College of Medicine in New York City.
The new type of coronavirus that causes a condition found in other cardiovascular diseases is called endothelial dysfunction. Santulli, who wrote about the idea in the spring, says that may be the “cornerstone” of organ dysfunction in patients with COVID-19.
“The common denominator in all these COVID-19 patients is endothelial dysfunction,” he said. “It’s like a virus that knows where to go and knows how to attack these cells.”
The runaway immune response adds to the plot
A major source of damage to the vascular system may also stem from the body’s own fleeing immune response to the new coronavirus.
“What we see with SARS-CoV-2 is actually the degree,” said Yogen Kanthi, cardiologist and vascular medicine specialist at the National Institutes of Health who is studying this stage of the disease. unprecedented inflammation in the blood.
“This virus is capitalizing on its ability to induce inflammation, and that is leading to nefarious, harmful effects.”
When inflammation spreads through the inner lining of blood vessels – a condition called endometritis – blood clots can form throughout the body, starving tissues of oxygen and even promoting inflammation. more.
“We begin this constant, self-amplifying inflammatory cycle in the body, which can then lead to more blood clotting and more inflammation,” Kanthi says.
Another indication of endothelial damage comes from blood analysis in patients with COVID-19. A recent study found that elevated levels of a protein produced by endothelial cells, called the Von Willebrand factor, are involved in blood clotting.
“They are passed through the roof,” said Alfred Lee, a hematologist at the Yale Cancer Center who co-commissioned research with Hyung Chun, a cardiologist and vascular biologist at Yale. severe illness.
Lee points out that certain autoimmune diseases can lead to an interplay of blood clotting and inflammation known as immune thrombosis.
Chun says elevated levels of the Von Willebrand factor suggest vascular damage can be detected in patients while in hospital – and possibly even before, this could help predict how likely they will develop. more serious complications.
But he said it remains unclear what is the driving force leading to vascular damage: “It seems that this is the progression of the disease that actually caused this endothelial damage; the key question is the root cause of this. what?”
After they presented their data, Lee said Yale’s hospital system had begun to bring aspirin patients seriously ill with COVID-19, which could prevent blood clots. While the best combinations and dosages are still being studied, research indicates that blood thinners may improve outcomes in patients with COVID-19.
Treatments are also being investigated, Chun said, that may provide more direct protection of endothelial cells from coronavirus.
“Is that the end of COVID-19 treatment? I totally don’t think so. There are many aspects of the disease that we still do not fully understand.
COVID-19 serves as a blood vessel “ stress test ” for people with pre-existing vascular problems.
Early in the pandemic, Roger Seheult, a critical care physician and lung disease in Southern California, realized that the patients he expected were the most susceptible to respiratory viral infections, those with the disease. Latent lung disease such as chronic obstructive pulmonary disease and asthma, are not patients who end up disproportionately in their intensive care unit.
“Instead, what we’re seeing are obese patients, people with large BMIs, people with illnesses,” said Seheult, who runs the popular medical education website MedCram. type 2 diabetes and high blood pressure. “
Over time, all of those conditions can cause inflammation and damage to the lining of blood vessels, including a harmful chemical imbalance known as oxidative stress, he said. Seheult says coronavirus infection becomes an added stress for people with blood vessel medical conditions.
“If you were at the edge and you were blown away by the wind from this coronavirus, then you have crossed the edge.”
He said that extensive damage to the blood vessels could explain why COVID-19 patients with severe respiratory problems are not necessarily the same as those with the flu.
“They are having trouble breathing, but we have to realize that the lungs are not just the airways,” he said. “It’s a problem with the blood vessels themselves.”
This is why COVID-19 patients struggle to supply oxygen to their blood, even when air is being pumped into their lungs.
“Endothelial cells leak out, so instead of being like the Saran Wrap, it turns into a sieve and then it allows fluids from the blood stream to accumulate in space,” says Harvard’s Libby.
COVID-19 doctors are now acutely aware that complications such as stroke and heart problems can occur, even after the patient gets better and their breathing improves.
“They have run out of oxygen, they can be discharged home, but their blood vessels are still not fully resolved, they are still inflamed,” he said. “It can happen that they develop a blood clot and they have large pulmonary embolism.”
Patients may be closely monitored for these problems, but one of the major unknowns for both the physician and the patient is the long-term effect of COVID-19 on the circulatory system.
Li of the Angiogenesis Foundation says this: “The virus enters your body and it leaves your body. You may or may not have been ill. But is that leaving a vascular system littered? “
This story comes from NPR’s partnership with Kaiser Health News.