It’s still completely unknown how Covid-19 causes clots.It might be doing this indirectly, by ramping up inflammation throughout the body. Or it could be infecting the lining on the insides of blood vessels. These endothelial cells regulate how much fluid can flow into each vessel, and help coordinate the clotting response after injury. The virus could end up making these cells send out their clotting signals inappropriately. Covid-19 might also be causing blood problems via the adaptive immune response, Cunningham says. He wonders whether immune cells that are specifically targeted to the Covid-19 virus in later stages of infection are involved in clotting.

There are further wrinkles. For one thing, blood clots linked to Covid-19 aren’t being seen as much in some countries as others, according to neurologist Thirugnanam Umapathi of Singapore’s National Neuroscience Institute. Umapathi, who lost a colleague to SARS in 2003, was among the researchers who called attention to the risk of clotting during that outbreak. So far he hasn’t heard about this happening in his country to the same degree with Covid-19. “The jury is still out” as to why, Umapathi says. The complication has also been more evident among those with the most severe cases of disease. This was known as far back as February, when doctors in Wuhan, China, reported that among 183 people hospitalized with the disease, more than two-thirds of those who died had abnormal clotting. That’s compared with less than 1 percent of those who survived.

Health workers treating Covid-19 patients have been astonished to see that patients on anticoagulants still develop clots, according to Dimitrios Giannis, a doctor and health outcomes researcher at Northwell Health’s Feinstein Institute for Medical Research in Manhasset, New York. The hospital system he is affiliated with is planning a clinical trial to see how different doses of blood thinners might be used to prevent or treat clotting in this pandemic disease, and others such studies are already underway elsewhere. But these drugs can have side effects, such as bleeding, and must be administered carefully. Meanwhile, other places are trying to bust up Covid-19-associated clots with tissue plasminogen activator, a drug normally deployed against strokes and heart attacks.

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Giannis says that once he started looking into the phenomenon, he was surprised to find published papers on blood-clot risks associated with SARS and MERS. “We found out many similarities with previous coronaviruses—things we didn’t even know were reported previously. So, it was a good lesson to study all the literature and identify all the relevant studies.”

In the meantime, researchers with a long-standing interest in the link between respiratory diseases and blood clots have been given a chance to extend their work in vital ways. Until now, it’s been very tricky to observe the link between infections and clots in real-time. For example, virologist Marco Goeijenbier had tried, in recent years, to study whether people with influenza are more prone to abnormal clotting. Despite the ubiquity of flu, there were still not enough cases around for him to get that project off the ground. Now he is treating patients with Covid-19 at the Netherlands’ Erasmus Medical Center in Rotterdam, and “the numbers are high enough” for proper research.

Goeijenbier has been pleased to see other researchers coming around to the importance of the link between pathogens and clotting. That wasn’t always the case: “I got papers rejected with the editor saying that it’s not relevant,” he says. The link has always mattered, though, regardless of the “relevance” assigned to it. For instance, there are signs that efforts to control the spread of influenza also help protect cardiovascular health. An analysis of 30 million patient records presented last spring at the American College of Cardiology meeting calculated—after accounting for factors such as age and gender—that getting a flu shot could reduce a person’s risk of heart attack from clogged coronary arteries over the following year by 10 percent. It’s one of many studies that have found this kind of protective effect. This only makes the study of clotting in Covid-19 more urgent. Who knows—finding ways to prevent blood abnormalities in this pandemic might prove useful in avoiding similar complications from other infections. If we unlock the mystery of today’s “strange blood problem,” we might be better equipped to fight other viruses in the future.

Photographs: Volker Brinkmann/Getty Images; Dea Picture Library/De Agostini/Getty Images

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