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As doctors treat more and more COVID-19 patients, they are realizing the new coronavirus can affect far more than just a patient’s lungs. And with a vaccine still months or years away, researchers say effectively treating these complications could help save lives.
Neurosurgeon Pascal Jabbour treats stroke patients, people with blood clots blocking blood flow to their brains, at Jefferson Health in Philadelphia. These are urgent cases that get flown in by helicopter. He has a very little time to go into the patient’s blood vessels to try and reverse the clot.
“Usually when a stroke comes in, we go in quickly … open the vessel,” Jabbour said. “In general, they do well.”
For the past few weeks, some of those stroke patients come in with COVID-19, and others turn out to be positive after being tested. Jabbour said quite a few of those cases don’t end well.
“Even though we’re opening the vessel, they are … dying,” in many cases from lung complications, he said.
He investigated the overlap between strokes and COVID-19 with a colleague at New York University in a journal article that is under review. They found that around 30 to 40% of people coming into hospitals with strokes also have COVID-19. Of the 12 patients in their study, half of them died.
Abnormal blood clots
Jabbour and other doctors say COVID-19 is causing a lot of abnormal blood clots around the brain, heart and blood vessels in general. This is such a big problem that medical staff at Jefferson are thinking about preemptively starting COVID-19 patients on blood thinners, according to Jabbour.
Among a group of COVID-19 patients in intensive care at the University of Colorado Anschutz Medical Campus, some “are literally clotting off every blood vessel in their body,” said transplant surgery fellow Hunter Moore. He added these patients’ blood clots are not breaking down, so 30% of them have strokes, and half of them have blood clots blocking blood flow to the lungs.
A Dutch study of 184 COVID-19 patients in intensive care in three hospitals found that a “remarkably high” 31% had blood clotting complications. This builds on similar early findings from Wuhan, China.
What does a virus that causes breathing problems have to do with blood clots?
Scientists have yet to understand this fully, but here are the main ideas, according to Adam Cuker, a hematologist and associate professor of medicine at the University of Pennsylvania:
When someone becomes infected with the new coronavirus, or really anything that could be harmful, the body starts an inflammatory response. Scientists know there is a connection between inflammation and blood clotting, such as the release of more blood-clotting proteins, hence the higher risk of abnormal blood clots in COVID-19 patients.
The new coronavirus can also infect the cells that line the blood vessels. The body treats that as an injury, so the blood starts clotting.
“That makes good sense from an evolutionary perspective because if we were to cut ourselves, we want a clot to form at the site of injury,” Cuker said. “But in this situation, that adaptive response goes too far, and ends up putting the patient at great risk for pathological clotting.”
He added that doctors at Penn Medicine are sufficiently worried about blood clotting issues continuing after COVID-19 patients are discharged, so they are sending some patients out with medication for it.
Regina Marston returned to her California home from a trade show in Las Vegas in January with a bad cough, a fever and chills. She later developed a dull pain in her lungs on the right side, and a scan revealed a blood clot.
“I had so much pain … I still can’t lay on my right side,” she said. “I’m not comfortable laying flat, I still … wake up a lot throughout the night.”
Her doctor put her on blood thinners for five weeks, and she is now being tested for COVID-19.
Is it a heart attack or not?
COVID-19 can also mimic a heart attack, either through inducing inflammation of the heart muscle, or possibly causing tiny blood clots. It’s not entirely clear how, said Jay Giri, a cardiologist at the University of Pennsylvania. This has come up enough that doctors at Penn Medicine have changed their procedures in emergency rooms slightly.
Usually, when an emergency room doctor sees a certain pattern on an electrocardiogram, doctors diagnose a heart attack, and the patient gets rushed to a cardiology procedure suite right away. It’s not uncommon for heart attack patients to have trouble breathing, sometimes even requiring a breathing tube, so doctors can’t always ask a patient what is going on with their symptoms.
“We’re just so used to rushing the patient into the procedures suite … in minutes, no question, find a blocked up blood vessel that we’re rushing to open to stop (the) heart attack,” Giri said.
But during the pandemic, doctors sometimes find there is no blockage. A lab test leads to a COVID-19 diagnosis.
“Before, it’s like you drop the phone and you’re running to your car. Now at least you’re having a one minute conversation: Does the patient have a fever? … And then that would raise your suspicion of COVID.”
Some doctors learned about the excessive blood clotting problem with COVID-19 from observing patients in the ICU who needed dialysis to replace part of their kidney function, said Michael Connor, an associate professor of medicine at Emory University specializing in critical care medicine and nephrology, the study of the kidneys.
He explained that in blood, there is a fine balance between clotting and not clotting. Doctors noticed that even compared to other ICU patients on dialysis, COVID-19 patients had more blood clotting.
Nephrologists are thinking of new ways to manage this issue, said Jorge Cerda, professor of medicine at Albany Medical College in New York.
Cerda, who is also chief of medicine for St. Peter’s Hospital in Albany, said that nephrologists are “very used to using blood thinners,” but “none of them work well” in this case.
“So we had to invent other ways … perhaps use two different kinds of anticoagulants, so this is a key, evolving problem.”
Cerda, Connor and a group of specialists at the American Society of Nephrology have drafted recommendations for how to manage COVID-19 related kidney injuries, to be published in the society’s main journal.
The coronavirus also affects the kidneys. Early research from China shows that about 5% of COVID-19 patients needed kidney support, and kidney disease is associated with COVID-19 deaths, said Cerda.
One possible explanation is that the virus binds to a specific kind of receptor in cells, and the kidney has those receptors.
The inflammation, excessive blood-clotting and shock from COVID-19 can affect the kidneys to the point of requiring dialysis for patients. Cerda added that, fortunately, patients can recover.
Connor pointed out this means with all the talk about how many ventilators states have, they should also be watching the number of dialysis machines. New York has already reported shortages.
Ideas for short-term treatments
Knowing that COVID-19 is linked to abnormal blood clots also points to potential short-term treatments, so fewer patients die of blood clots that lead to organ failure.
The University of Pennsylvania is one of several sites in an upcoming clinical trial to see how COVID-19 patients do on different doses of heparin, a blood thinner, according to hematologist Adam Cuker.
Another group of researchers is working on a forthcoming trial of tPA, a drug used to break up or dissolve blood clots as an emergency treatment of strokes and heart attacks, to see how it does with COVID-19 patients.
That group includes Christopher Barrett, resident physician in general surgery at Beth Israel Deaconess Medical Center and visiting scientist at MIT. Barrett said organ failure is what’s killing patients.
“Their immune system in most, not all, but in most patients will eventually clear the virus, but they cannot do that if they’re dying of organ failure first,” he said. “We may be months or even a year away from effective antiviral therapy or or vaccines, and so a lot of the early gains that you’re going to see in changing people’s outcomes are going to come from critical care.”