What's bleeding in the car

Corona: Why the blood clumps with Covid-19

Surprising finding: Researchers have found out why the blood of many Covid-19 patients clumps so strongly. The cause is therefore not the coronavirus itself, but an autoimmune reaction of the body's own defense. This leads to a massive release of special antibodies that attack white blood cells and cause the blood to clump. This knowledge could open up new therapeutic opportunities for Covid-19.

The coronavirus attacks almost the entire body, that much seems clear now. One of the components particularly affected are the blood vessels and blood. Since the beginning of the corona pandemic, doctors have been observing that a striking number of Covid 19 patients suffer from excessive blood clotting. Thromboses, pulmonary embolisms and also strokes are the frequent consequences.

"In patients with Covid-19 we see a relentless, self-reinforcing vicious circle of inflammation and clumping of the blood throughout the body," explains Yogendra Kanthi of the University of Michigan.

Similarity to an autoimmune disease

But so far it has remained largely unclear what causes this excessive coagulation - the virus itself, infection-related inflammation of the vessels or an immune reaction? "Most patients have normal levels of clotting factors, fibrinogen and platelets, suggesting that Covid-19 causes a unique prothrombotic condition," say Kanti, colleague Yu Zuo and her team.

Interesting, however: In some respects, the increased tendency to thrombosis of Covid-19 patients is similar to an autoimmune disease, which can also lead to fatal clumping of the blood, as the researchers explain. In this so-called antiphospholipid syndrome, the body mistakenly makes antibodies against some blood components, including phospholipids and phospholipid-binding proteins. The accumulation of antibodies on these molecules causes the blood to clump.

Typical auto-antibodies also in Covid-19 patients

Could something similar also be the case with Covid-19? To find out, the scientists analyzed the blood of 172 hospital-treated Covid-19 patients with severe disease. They specifically searched for eight antibodies that are typical of the antiphospholipid syndrome.

The result: "A good half of the Covid 19 patients were positive for at least one of these auto-antibodies," reports senior author Jason Knight. A quarter of the patients had two or more of these ApL antibodies. There were clear correlations with the clinical course of Covid 19 disease: the higher the titer of the auto-antibodies in the patient's blood, the more severely the kidneys, lungs and blood were affected.

Found guilty party?

Such a clear connection between the auto-antibodies and the severity of the Covid-19 course was unexpected, says Kanthi. "This suggests that these auto-antibodies could be the culprit in this vicious circle of blood clots and inflammation that makes many Covid patients so sick." Apparently, infection with SARS-CoV-2 directly or indirectly promotes the production of these misdirected antibodies and thus derail the blood clotting.

This is supported by the observation that such patients often have white blood cells that are overactivated by the antibodies, as Kanthi and his colleagues explain. These immune cells then produce extracellular fibers, so-called neutrophil extracellular traps (NET), which form a kind of network. Usually they help fight bacteria, but in this case they make the blood clumping even more.

Antibodies from patients cause mouse blood to clump together

In order to check whether the antibodies of the Covid patients are actually the cause of the excessive tendency to thrombosis, the scientists carried out a supplementary experiment with mice. In these cases they had previously increased the risk of thrombosis due to a slight narrowing of the large vena cava. They then isolated the ApL antibodies from some Covid-19 patients and injected the animals with the purified, cell-free extract.

It showed: "The antibodies of the patients with an acute Covid-19 disease produced an astonishing extent of thrombosis in the animals - some suffered from the most severe blood clots that have ever seen," says Kanthi. At the same time, he and his team were able to demonstrate the noticeable overactivation of the white blood cells and the extracellular networks in the mice. "We have thus identified a new mechanism that causes blood clots in Covid 19 patients," said the researchers.

Opportunities for better therapies

The current findings also open up new opportunities for better treatment of this derailed blood coagulation. Because in addition to the anticoagulant heparin, which is also administered in many Covid 19 cases, the antiphospholipid syndrome is also treated with the active ingredient dipyridamole. "This is an old drug that is safe, cheap and widely available," says Kanthi.

Initial tests now suggest that this agent could also help with Covid-19. That is why the research team has already started a clinical study with dipyridamole. They also recommend checking the effectiveness of a so-called plasmapheresis - blood washing in which certain components of the blood are filtered out in a targeted manner. (Science Translational Medicine, 2020; doi: 10.1126 / science.abd3876)

Source: Michigan Medicine - University of Michigan

November 6, 2020

- Nadja Podbregar