Autoantibodies and over-active neutrophils may be cause of COVID-19 blood clots

One of the most life-threatening complications associated with severe COVID-19 is the appearance of blood clots in the arteries, veins and microscopic vessels. These occur in approximately half of all patients with severe symptoms and have been shown to trigger strokes and impair oxygen exchange by restricting blood flow in the lungs. However, exactly what causes these clots to appear was unknown.

In a new paper published in Science Translational Medicine, researchers found that a particular type of autoantibody (antibody that attacks the body’s own tissue) causes these clots. According to the team these particular antibodies are typically seen in patients with an autoimmune condition called antiphospholipid syndrome.

“In patients with COVID-19, we continue to see a relentless, self-amplifying cycle of inflammation and clotting in the body,” explained co-corresponding author Dr Yogen Kanthi, an assistant professor at the Michigan Medicine Frankel Cardiovascular Center and a Lasker Investigator at the National Institutes of Health’s National Heart, Lung, and Blood Institute, both US. “Now we’re learning that autoantibodies could be a culprit in this loop of clotting and inflammation that makes people who were already struggling even sicker.”

In their paper the team report that half of the severely ill, hospitalised COVID-19 patients in their study had a combination of high levels of both the dangerous antibodies and super-activated neutrophils, a type of white blood cell known for their destructive properties. In April, the team was the first to report that patients hospitalised for severe COVID-19 had higher levels of neutrophil extracellular traps (NETs) in their blood.

To ascertain whether this combination of neutrophils and autoantibodies were the cause of the blood clots the team studied them together in mouse models.

“Antibodies from patients with active COVID-19 infection created a striking amount of clotting in animals – some of the worst clotting we have ever seen,” Kanthi reported. “We have discovered a new mechanism by which patients with COVID-19 may develop blood clots.”

Combatting the blood clots

The authors said that while their findings are not ready for clinical practice, they reveal a lot about thrombosis and inflammation in patients with COVID-19.

The team said that based on the results, severely ill patients with high levels of these autoantibodies would have superior outcomes if the antibodies are blocked or removed. To accomplish this, aggressive techniques such as plasmapheresis, which is commonly used in severe autoimmune diseases, may need to be used. Plasmapheresis involves draining blood through an IV, filtering it and replacing it with fresh plasma that does not contain the self-reactive antibodies associated with blood clots.

“We know people with the highest levels of autoantibodies did worse in terms of respiratory function and the antibodies caused inflammation even in healthy cells,” said first author of the study, Dr Yu (Ray) Zuo, an assistant professor of internal medicine and a rheumatologist at Michigan Medicine.

The researchers said the next step in research would be to conduct additional research to identify what triggers the production of the autoantibodies and what they target.

This group is also currently running a randomised clinical trial called DICER, which is testing a US Food and Drug Administration (FDA)-approved anti-clotting agent, dipyridamole, in patients with COVID-19 to determine whether it is more effective than a placebo in reducing excessive blood clots and inflammation.