Picture a skating rink before a hockey match. The top layer of ice is glassy and slick. The players and pucks glide smoothly across. Dr. William Li says that ice is like the lining of your blood vessels when you're healthy.
But during a coronavirus infection?
“The virus damages the inside of the blood vessel and shreds the lining,” Li says. “That's like the ice after a hockey game.”
The lining becomes ragged and leaky. Things start to get stuck, “and you wind up actually having this situation which is really untenable for blood flow,” he says.
Li and an international team of researchers compared the lung tissue of people who died from COVID-19 with those who died from influenza. They found stark differences. For example, the COVID lungs had nine times as many tiny blood clots.
“The surprise was that this respiratory virus that gets into the lung makes a beeline for your vascular endothelial cells, the cells lining blood vessels,” Li explains.
These endothelial cells are a vital part of the vascular system, coating the inside wall of every artery, vein and capillary. If the coronavirus is wreaking a special kind of havoc on the endothelial cells, as Li and other scientists think, that helps explain why COVID complications can appear anywhere in the body.
“The effects in the brain, the blood clots in the lung and elsewhere and in the legs, the COVID toe, the problem with the kidneys and even the heart,” he says.
Early in the pandemic, Dr. Gaetano Santulli saw how many different organs could be affected, and he suspected endothelial cells might hold the key. Santulli, a researcher at Albert Einstein College of Medicine in New York City, says to consider what these endothelial cells do in a healthy person.
“Mainly, the endothelial cell function is to avoid high blood pressure and to avoid blood clotting,” Santulli says.
But when these cells don't work properly, the opposite can happen. Santulli saw this with COVID.
“If there is endothelial dysfunction because of the virus, we can explain why we have an increased risk of blood clotting in COVID-19 patient,” Santulli says.
Scientists aren't sure how COVID damages blood vessels. What's clear is the body's immune response often begins to spiral out of control.
“What we see with the SARS-2 coronavirus is really an unprecedented level of inflammation in the bloodstream,” says Dr. Yogen Kanthi of the National Institutes of Health. “We start to get this relentless, self-amplifying cycle of inflammation in the body. And that may lead to clotting.”
This is most striking in severe cases of COVID. And physicians who care for these patients, like Dr. Roger Seheult, have come to see COVID as a vascular disease in addition to a respiratory illness.
Seheult is a critical care and pulmonary physician in Southern California. Early in the pandemic, he noticed the patients who ended up in the intensive care unit tended to have diabetes, high blood pressure or were obese. All those conditions can damage the blood vessels and cause inflammation.
“It's a stress test,” Seheult says. “If you're right on the edge and you get the wind blown from this coronavirus, now you've gone over the edge.”
He also noticed that the patients hospitalized with COVID are different from those hospitalized for respiratory viruses like the flu.
“They are having shortness of breath, but we have to realize that the lungs are more than just the airways. It's an issue with the blood vessels themselves,” Seheult says.
That's why COVID patients can struggle to get enough oxygen, even if air is being pumped into their lungs by a ventilator. Seheult says even after breathing improves, some patients still have damaged blood vessels.
“They're now off oxygen. They can be discharged home. But their vasculature is not yet completely resolved. They still have inflammation,” he explains.
So what does this mean for COVID treatment? Doctors are already using drugs to manage inflammation and prevent clots, though they're still working out the best combinations and dosages. They're also looking at more direct ways of protecting endothelial cells to prevent blood vessels from breaking down.