Are antibodies to blame for the thrombosis?

Blood clots

A common complication with Covid-19 is increased blood clotting. (Image: Robocop / iStok)

The infection with Sars-CoV-2 not only attacks the lungs and many organs, it also causes the blood to clump and thrombosis. Researchers could now have found out why the blood coagulation derailed in Covid-19. Accordingly, the coronavirus is not the direct cause, 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.

In the course of the corona pandemic, it is becoming increasingly clear that the Sars-CoV-2 coronavirus attacks various organs and tissues in our body. In addition to the airways and lungs, the kidneys, intestines, heart and nervous system are also affected. A consequence of the disease that occurs particularly frequently in Covid 19 patients is an increased tendency for the blood to clot. In autospia of deceased patients, doctors found a surprising number of thromboses and blood clots in arteries, veins and also capillaries. Pulmonary embolisms are also a common and often fatal complication. “In patients with Covid-19 we see a relentless, self-reinforcing vicious circle of inflammation and clumping of the blood throughout the body,” explains co-author Yogendra Kanthi of the University of Michigan. In the meantime, people with a severe course of Covid-19 in the intensive care unit are usually given preventive anticoagulant drugs such as heparin.

Similarity to Autoimmune Disease

Why the infection with the coronavirus triggers this blood coagulation derailment has so far remained unclear. Because the characteristics of this excessive coagulation are different from those previously known: “Most patients have normal concentrations of blood coagulation factors, fibrinogen and platelets, which suggests that Covid-19 causes a unique prothrombotic condition”, explain Kanthi and his colleagues. Theoretically, this could be due to a direct effect of the virus, but also to inflammation of the blood vessels or disorders in the biochemical regulation of blood coagulation. The body’s immune response to the infection could also cause this phenomenon.

This is where the study by Kanthi, first author Yu Zuo and her colleagues comes in. Because, as they explain, the excessive thrombosis tendency of Covid-19 patients is similar to an autoimmune disease, which can also lead to fatal clumping of the blood. In this so-called antiphospholipid syndrome, the body mistakenly makes antibodies against some molecular components of the blood, including phospholipids and phospholipid-binding proteins. The accumulation of antibodies on these molecules causes the blood to clump. To find out whether something similar might also happen with Covid-19, the scientists analyzed the blood of 172 Covid-19 patients treated in hospital with a severe course. They searched specifically for eight antibodies that are typical of the antiphospholipid syndrome – and found what they were looking for: “A good half of the Covid 19 patients were positive for at least one of these auto-antibodies,” reports senior author Jason Knight from the University of Michigan. The higher the titer of these auto-antibodies in the patient’s blood, the more severely the kidneys, lungs and blood were affected.

Antibodies exposed as culprits

“This suggests that these auto-antibodies could be the culprit in this vicious circle of blood clotting and inflammation that makes many Covid patients so sick,” says Kanthi. To check this, 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. In fact, the mice then also showed the typical Covid clumping tendency: “The antibodies of the patients with acute Covid-19 disease produced an astonishing degree of thrombosis in the animals – some suffered from the most severe blood clotting that they have ever seen,” says Kanthi. At the same time, he and his colleagues observed a noticeable overactivation of the white blood cells in the animals, which then form networks of extracellular fibers and thus further promote the clumping. Such so-called Neutrophil Extracellular Traps (NET) have also been observed in Covid-19 patients.

“We have thus identified a new mechanism that causes blood clots in Covid 19 patients,” the researchers state. The current findings now open up new opportunities for a better treatment of this derailed blood clotting. 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. “It’s 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.

Source: Yu Zuo (University of Michigan, Ann Arbor) et al., Science Translational Medicine, doi: 10.1126 / science.abd3876)
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