Covid-19 Are antibodies responsible for thrombosis?


Sars-CoV-2 infection not only attacks the lungs and many organs, but also causes blood clots and thrombosis. Researchers could now have discovered why blood clotting derailed in Covid-19. Consequently, 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 blood to pool. This knowledge could open up new therapeutic opportunities for Covid-19.

Over the course of the corona pandemic, it is 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 patients with Covid 19 is an increased tendency for blood to clot. In the autospy of deceased patients, doctors found a surprising number of thromboses and blood clots in arteries, veins and even capillaries. Pulmonary embolism is also a common and often fatal complication. “In patients with Covid-19, we see a relentless, self-reinforcing vicious cycle of inflammation and blood clumping throughout the body,” explains University of Michigan co-author Yogendra Kanthi. Meanwhile, people with a severe course of Covid-19 in the intensive care unit are usually given preventative anticoagulant drugs such as heparin.

Similarity to autoimmune disease

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

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

Antibodies exposed as culprits

“This suggests that these autoantibodies could be the culprits of this vicious circle of blood clotting and inflammation that makes many Covid patients sick,” says Kanthi. To verify this, the scientists conducted an additional experiment with mice. In these cases, they had previously increased the risk of thrombosis due to a slight narrowing of the greater vena cava. Then they isolated ApL antibodies from some Covid-19 patients and injected the animals with the purified, cell-free extract. In fact, the mice also showed the typical Covid agglomeration tendency: “Antibodies from patients with acute Covid-19 disease produced a surprising degree of thrombosis in animals – some suffered from the more severe blood clotting than that. have ever seen, “Kanthi says. At the same time, he and his colleagues observed a noticeable hyperactivation of white blood cells in animals, which then form networks of extracellular fibers and thus further promote aggregation. Such so-called Neutrophil Extracellular Traps (NETs) have also been observed in patients with Covid-19.

“We have thus identified a new mechanism that causes blood clots in patients with Covid 19,” say the researchers. The current findings now open up new opportunities for better treatment of this derailed blood clotting. Because in addition to the heparin anticoagulant, which is also administered in many cases of Covid 19, the antiphospholipid syndrome is also treated with the active ingredient dipyridamole. “It’s an old drug that’s 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 trial with dipyridamole.

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

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