In COVID-19, autoimmune antibodies can cause blood clots

A new study shows that the novel coronavirus can induce the generation of autoantibodies that cause clots. The high incidence of blood clots among COVID-19 patients can be explained by this result.

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Alongside the respiratory characteristics of COVID-19, thromboses, better known as blood clots, have been encountered by many people with the disease.

Some estimates indicate that in 30 percent of critically ill patients, the novel coronavirus triggers blood clots which can lead to severe complications, including strokes.

These results also prompted researchers to evaluate whether for example, existing blood-thinning drugs usually used to prevent blood clots after a heart attack could improve outcomes for individuals with COVID-19. However it remains unknown exactly what causes blood clots to form in individuals with the disease.

New research led by a University of Michigan team indicates that in people with COVID-19, a form of autoantibody normally seen in people with the autoimmune disease antiphospholipid syndrome may be behind blood clots.

In more than half of the COVID-19 patients, the researchers identified clot-causing antibodies in their study, and these antibodies were also associated with impaired renal function.

The research could lead to new strategies for treatment and can be found in the journal Science Translational Medicine.

aPL autoantibodies

Different explanations for the presence of blood clots in people with COVID-19 have been suggested by scientists, including the ‘cytokine storm’ caused by an excessive immune response, blockages of blood vessels caused by very low levels of oxygen and direct damage to blood vessels caused by SARS-CoV-2, the virus responsible for COVID-19.

However the current research explored a new mechanism involving a form of antibody called an autoantibody, which targets the body’s lipids.

These antibodies are a part of the autoimmune disorder antiphospholipid syndrome, which is associated with blood clots in the veins and arteries, known as antiphospholipid (aPL) autoantibodies.

APL antibodies activate the blood clotting process by activating different factors in the blood, including platelets. Viral infections may lead to these antibodies being formed, including the infection that causes COVID-19, according to recent case reports.

However, there is still limited evidence on aPL antibodies and their ability to cause blood clots in individuals with COVID-19. To add to the facts, this study tested 172 people receiving COVID-19 in-patient care for aPL antibodies.

More than half of the patients

The researchers found that more than half of the patient samples contained autoantibodies of aPL, using the threshold recommended by the manufacturer of the test. They also found evidence to support the hypothesis that in COVID-19 patients, the antibodies may cause blood clots.

More platelets and the release of neutrophil extracellular traps (NETs) were related to higher levels of the antibodies. The process of blood clotting is activated by platelets, and NETs are sticky webs that help capture viruses, but also facilitate blood clot formation.

The team also found that antibodies taken from patients with COVID-19 triggered the release of NETs in healthy individuals’ blood samples and caused the formation of blood clots in two mouse models when injected into mice.

Co-author Dr. Yogendra Kanthi, a cardiologist and specialist in vascular medicine at the University of Michigan, says: “Antibodies from patients with active COVID-19 infection developed a large amount of clotting in animals, some of the worst clotting we have ever seen.”

The researchers claim they have identified a new mechanism by which blood clots can form in patients with COVID-19.

The aPL antibodies were also associated with reduced kidney function, and worse respiratory function was associated with some, though not all, aPL antibodies. This indicates that blocking these antibodies may enhance patient outcomes.

In terms of respiratory function, people with the highest levels of autoantibodies fared worse and the antibodies triggered inflammation even in healthy cells,’ states Dr. Yu Zuo, a rheumatologist and assistant professor of internal medicine at the university, first author.

Blocking the antibodies

In the hope of discovering a cure, researchers are now researching what could cause the body to generate the antibodies in the first place.

They note that plasmapheresis, which involves filtering the blood to remove the clot-causing antibodies and replacing them with plasma that does not contain the antibodies, may benefit patients. This rather intensive care, however is commonly reserved for individuals with serious autoimmune disorders.

In addition, the team is studying an established blood thinner called dipyridamole (Persantine), which prevents the formation of blood clots.

“Dipyridamole is an old drug that is safe, inexpensive, and scalable,” explains Dr. Kanthi. “It was approved 20 years ago by the [Food and Drug Administration] to prevent clotting, but we have only recently discovered its ability to inhibit this particular form of inflammation in [people with COVID-19].”

A clinical trial to assess the use of dipyridamole in people with dipyridamole has already begun, and the researchers plan to report the findings early next year.

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