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Whether it’s strange rashes on the toes or blood clots in the brain, the widespread ravages of COVID-19 have increasingly led researchers to focus on how the new coronavirus sabotages the body’s blood vessels.
As scientists have come to understand the disease better, they have focused on the vascular system – the body’s network of arteries, veins and capillaries, which stretches more than 60,000 miles – to understand this wide-ranging disease and, with luckily, find treatments that can hinder its most pernicious effects.
Some of the first ideas on how COVID-19 can act as a vascular disease came from studying the aftermath of the most serious infections. Those reveal that the virus deforms a critical piece of our vascular infrastructure: the single layer of cells that lines the inside of each blood vessel, known as endothelial cells or simply endothelium.
Dr. William Li, a vascular biologist, likens this coating to a freshly resurfaced ice skating rink before a hockey game, where players and pucks glide smoothly.
“When the virus damages the inside of the blood vessels and destroys the lining, it is like ice after a game of hockey, “says Li, researcher and founder of the Angiogenesis Foundation.” You end up with a situation that is really unsustainable for blood flow, “he says.
In a study published this summer, Li and an international team of researchers compared the lung tissues of people who died from COVID-19 with those who died from influenza.
They found big differences: the lung tissues of the COVID patients had nine times smaller blood clots (“micro thrombi”) compared to those of the influenza patients, and the coronavirus-infected lungs also had “severe endothelial lesions.”
“The surprise was that this respiratory virus goes straight into the cells that line the blood vessels, filling them like a gumball machine and shredding the cell from the inside out,” says Li. “We found that the blood vessels are blocked and blood clots are forming due to damage to the lining.”
The new coronavirus is already known to break into cells through a specific receptor, called ACE2, which is found throughout the body. But scientists are still trying to understand how the virus triggers a cascade of events that causes so much destruction in blood vessels. Li says one theory is that the virus directly attacks endothelial cells. Laboratory experiments have shown that the coronavirus can infect human-engineered endothelial cells in lung tissue and other organs.
It is also possible that problems start elsewhere and endothelial cells suffer collateral damage along the way, as the immune system reacts, and sometimes overreacts, to the invading virus.
Endothelial cells have a host of important functions; These include preventing clotting, controlling blood pressure, regulating oxidative stress, and defending against pathogens. And, Li says that discovering how the virus endangers the endothelium may link many of the complications of COVID: “Effects on the brain, blood clots in the lung and elsewhere in the legs, the toe of COVID, the problem with the kidneys and even the heart. “
In Spain, skin biopsies of distinctive red lesions on the toes, known as “chilblains”, found viral particles in endothelial cells, leading the authors to conclude that “virus-induced endothelial damage could be the key mechanism. ”
Could the lining of our blood vessels be a common denominator?
With a surface area larger than a football field, the endothelium helps maintain a delicate balance in the bloodstream. These cells are essentially the “gatekeeper” of the bloodstream.
“The endothelium has developed a distant early warning system to alert the body to prepare for an invasion if there are problems,” says Peter Libby, a cardiologist and research scientist at Harvard Medical School.
When that happens, endothelial cells change the way they work, he says. But that process can also go too far.
“The same functions that help us maintain health and fight invaders, when they get out of control, can make disease worse,” says Libby.
In that case, the endothelial cells turn against their host and begin to promote clotting and high blood pressure.
“In COVID-19 patients, we have these two markers of dysfunction,” says Dr. Gaetano Santulli, a cardiologist and researcher at the Albert Einstein College of Medicine in New York City.
The new coronavirus triggers a condition seen in other cardiovascular diseases called “endothelial dysfunction.” Santulli, who wrote about this idea in the spring, says it may be the “cornerstone” of organ dysfunction in COVID-19 patients.
“The common denominator in all these COVID-19 patients is endothelial dysfunction,” he says. “It’s like the virus knows where to go and how to attack these cells.”
An uncontrolled immune response adds a twist to the plot
A major source of damage to the vascular system likely also comes from the body’s own uncontrolled immune response to the new coronavirus.
“What we see with SARS-CoV-2 is really an unprecedented level of inflammation in the bloodstream,” says Dr. Yogen Kanthi, a cardiologist and vascular medicine specialist at the National Institutes of Health, who is investigating this phase. of the illness.
“This virus is taking advantage of its ability to create inflammation, and that has these dire and deleterious downstream effects,” he says.
When inflammation spreads through the inner lining of blood vessels, a condition called endothelialitis, blood clots can form throughout the body, starving tissues of oxygen and further promoting inflammation.
“We start to have this cycle of incessant, self-amplifying inflammation in the body that can then lead to more clotting and more inflammation,” says Kanthi.
Another sign of endothelial damage comes from the blood test of COVID-19 patients. A recent study found elevated levels of a protein made by endothelial cells, called Von Willebrand factor, which is involved in clotting.
“They are through the roof for those who are critically ill,” says Dr. Alfred Lee, a hematologist at the Yale Cancer Center, who co-authored the study with Dr. Hyung Chun, a Yale cardiologist and vascular biologist.
Lee notes that some autoimmune diseases can lead to a similar interplay of clotting and inflammation, called “immunothrombosis.”
Chun says elevated von Willebrand factor levels show that vascular injury can be detected in patients while they are in the hospital, and perhaps even earlier, which could help predict their likelihood of developing more serious complications.
But he says it’s still unclear what the driving force behind the blood vessel damage is: “It seems to be disease progression that really brings out this endothelial injury, the key question is what is the root cause of this? ? “
After presenting his data, Dr. Alfred Lee says that the Yale hospital system began administering aspirin to patients who were seriously ill with COVID, which can prevent clotting. While the best combinations and dosages are still being studied, research indicates that anticoagulants can improve outcomes in COVID-19 patients.
Chun says treatments are also being studied that can more directly protect endothelial cells from the coronavirus.
“Is that the end of COVID-19 treatment? I don’t think so at all. There are so many aspects of the disease that we still don’t understand,” he says.
COVID as a vascular ‘stress test’ for people with pre-existing vascular problems
At the start of the pandemic, Dr. Roger Seheult, a pulmonary and intensive care physician in Southern California, realized that the patients he expected were most vulnerable to a respiratory virus, those with underlying lung conditions such as COPD and asthma, they weren’t the ones ending. disproportionately in your ICU.
Seheult, who runs the popular medical education website MedCram, says, “Instead, what we are seeing are obese patients, people who have a high BMI, people who have type 2 diabetes and high blood pressure.”
Over time, all of those conditions can cause inflammation and damage to the lining of blood vessels, he says, including a damaging chemical imbalance known as “oxidative stress.” Seheult says that infection with the coronavirus becomes an added stress for people with those conditions that already strain blood vessels.
“If you are at the limit and the winds of this coronavirus are blowing, now you have gone to the limit.”
He says the extensive damage to blood vessels could explain why COVID patients with severe respiratory problems do not necessarily look like patients who get sick with the flu.
“They have difficulty breathing, but we have to realize that the lungs are more than the airways,” he says. “It is a problem with the blood vessels themselves.”
This is why COVID patients struggle to fill their blood supply with oxygen, even when air is being pumped into their lungs.
“Endothelial cells are leaky, so instead of being like Saran Wrap, it becomes a sieve and then allows fluid from the bloodstream to pool in the air spaces,” says Libby of Harvard.
Doctors treating COVID are now well aware that complications such as strokes and heart problems can appear, even after the patient improves and their breathing improves.
“They don’t have oxygen, they can be discharged home, but their vasculature is not completely resolved, they still have inflammation,” he says. “What can happen is that they develop a blood clot and have a massive pulmonary embolism.”
Patients can be closely monitored for these problems, but one of the big unknowns for doctors and patients is the long-term effects of COVID on the circulatory system.
Li of the Angiogenesis Foundation puts it this way: “The virus enters your body and leaves your body. You may or may not have gotten sick. But is that leaving behind a shattered vascular system? “
This story comes from NPR’s partnership with Kaiser Health News.
