Illustration: Kieran Blakey

The Nuance

Aspirin May Treat Severe Covid-19 Disease, and That Tells Us Something Important

Aspirin may turn out to be a cheap and effective way to save lives and prevent lasting damage

Back in April, when the first wave of Covid-19 was crashing across the U.S., Michael Mazzeffi received an email from one of his colleagues at the University of Maryland Medical Center.

“One of our surgeons said that when he was drawing blood out of a patient, it literally clotted within five seconds,” says Mazzeffi, who is chief of the division of critical care anesthesiology. “It was pretty clear early on that patients with severe Covid had clotting disorders and that their blood was super coagulable.”

Clinicians around the world noticed this same clotting phenomenon. By mid-summer, autopsies of people who had died from Covid-19 revealed that their vasculature and organs were often suffused with clots and coagulated blood. “What we saw in the Covid ICU is that a lot of the patients would start developing a lot of clotting, and this high burden would lead to multi-organ failure and eventually death,” says Jonathan Chow, MD, an assistant professor of anesthesiology at the University of Maryland School of Medicine.

Because clotting seemed to be a signature of severe or damaging Covid-19 disease, Chow and Mazzeffi started to discuss whether aspirin — a blood-thinning drug that can block the formation of clots — could help improve outcomes. “Aspirin is a very potent antiplatelet agent,” Chow explains. Platelets are blood-cell fragments that, when activated, will clump together to form clots. “As soon as aspirin interacts with a platelet, that platelet becomes inactivated and can no longer participate in the clot-generating process,” he says.

For a study published on October 21 in the journal Anesthesia and Analgesia, Chow and Mazzeffi — along with a multi-university team of researchers — examined the effects of aspirin among people hospitalized with Covid-19. After adjusting their data to account for age, BMI, race, preexisting conditions, and other variables that could muddy their conclusions, they determined that the risk of death or ICU admission was almost halved among people who got aspirin compared to those who did not.

“This is now the second study linking blood thinners of some kind with improved outcomes,” Mazzeffi says. “I think it’s driving home the point that an important part of the disease’s process is clotting in the organs and that intervening in those pathways is something we should focus on.”

What this research tells us about the coronavirus

SARS-CoV-2 is a respiratory virus, and the illness it causes is often described as primarily respiratory in nature. But that’s turning out to be an oversimplification — especially for those who develop severe Covid-19 disease or symptoms that persist long after the initial infection has passed.

“It’s a whole-body virus,” says Girish Nadkarni, a doctor of internal medicine at the Mount Sinai Hospital in New York City. “It affects the kidneys, the brain, the blood vessels, and the heart. So it’s not just a respiratory virus.”

These anti-clotting and anti-inflammation benefits explain why plain old aspirin is such a widely deployed drug — and also why it may eventually prove helpful in treating Covid-19.

In July, Nadkarni and colleagues published a study in the Journal of the American College of Cardiology that looked at the effect of anticoagulant drugs on outcomes among hospitalized Covid-19 patients. Like the aspirin study that would follow a few months later, Nadkarni’s study found that anticoagulants significantly reduced the risk of death among certain groups of people with Covid-19. “We found that both prophylactic and therapeutic doses of anticoagulation led to a lower risk of intubation and mortality,” he summarizes.

Both his research and the aspirin study support the idea that — contrary to early assumptions — Covid-19 may be best characterized as a blood-vessel disease.

Follow-up work and confirmation studies are needed. But Nadkarni says that the idea that a blood-thinning drug like aspirin could protect people from Covid-19 is credible. “Aspirin and anticoagulant drugs both prevent clots, albeit in slightly different ways,” he explains. While aspirin shuts off the clot-forming activity of platelets, anticoagulant drugs act on clotting factors, which are proteins in the blood that help control the rate of bleeding.

Many common and lethal illnesses — including diabetes, heart disease, and several others that are associated with a heightened risk for severe Covid-19 disease — also promote blood coagulation and clotting, Nadkarni says. And along with helping to prevent clots, aspirin also combats inflammation, which is implicated in a wide range of medical conditions. Together, these anti-clotting and anti-inflammation benefits explain why plain old aspirin is such a widely deployed drug — and also why it may eventually prove helpful in treating Covid-19.

“The fact that [SARS-CoV-2] creates this hypercoagulable state is really fascinating because few other respiratory viruses do that to the same degree,” says Mazzeffi. He explains that there are specialized blood cells, called endothelial cells, that line the arteries, veins, and other blood-transporting vessels. “These endothelial cells maintain vascular integrity and help keep blood flow normal,” he says. “SARS-CoV-2 affects those cells and causes inflammation that may cause those cells to express things that cause clotting.”

The coronavirus and the disease states it causes are complex, he adds. But aspirin may turn out to be a cheap and effective way to save lives and prevent lasting damage.

“If someone becomes ill [with SARS-CoV-2] and their doctor says it’s safe for them to take aspirin, I think it’s reasonable for them to take it.”

Should at-risk people consider taking aspirin?

Doctors are usually hesitant to recommend a treatment that does not have a large body of evidence to support it. But Mazzeffi says that aspirin is such a familiar drug and its risks and safety profile are so well established that people who are exposed to the coronavirus may want to consider taking it in low doses.

“The good thing about aspirin is that it’s one of the best-studied drugs in the history of the Earth,” he says. “We know it’s not safe for everyone, but it’s taken by literally hundreds of millions of patients, and it has a great safety record.”

The greatest risk associated with aspirin is gastrointestinal bleeding. “If you have a history of peptic ulcers or bleeding from the stomach, then it may not be safe,” he says. Also, his study didn’t look at the effects of aspirin among children with SARS-CoV-2 — a group that already seems to be at low risk for severe Covid-19-related complications. “People shouldn’t be popping aspirin in kids,” he says.

But for most adults, taking a single low-dose (81 mg) aspirin pill each day for a period of a few weeks may be a low-risk, high-reward proposition.

“If someone becomes ill [with SARS-CoV-2] and their doctor says it’s safe for them to take aspirin, I think it’s reasonable for them to take it,” Mazzeffi says.

I write about health and science. I live in Detroit with my wife and kids. I’m trying to learn German, but my progress so far is nicht gut.

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