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Novel autoantibody sparks inflammation, blood clots in coronavirus patients

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Researchers in the United States have discovered a functional autoantibody in Covid-19 patients that contributes to the disease’s progression and the “firestorm” of blood clots and inflammation that it causes.

According to a growing body of research, Covid-19 mimics many aspects of systemic auto-immune disorders, including the release of a flurry of overactive immune cells that produce toxic webs of proteins and DNA known as neutrophil extracellular traps, or NETs.

For this study, the researchers examined serum from over 300 hospitalised Covid patients in search of a novel autoantibody that protects toxic NETs from destruction while also producing a long-lasting noxious effect in the patient’s body.

The findings, published in JCI Insight, show that many of the participants have significantly elevated levels of anti-NET antibodies. Those with higher levels of autoantibodies were more likely to experience severe Covid-19 symptoms.

“We see a slew of different antibodies produced in Covid-19 patients, and now we discovered another clinically significant one that is likely contributing to severe Covid,” said lead author Yu (Ray) Zuo, a rheumatologist at Michigan Medicine, University of Michigan.

“They feed into the inflammatory storm that we’re seeing in the most serious cases of viral infection,” Zuo added.

The NETs were created in the lab and incubated with Covid patient serum. They discovered that serum from patients with higher levels of anti-NET antibodies had difficulty degrading the toxic traps.

The researchers also supplemented healthy serum with anti-NETs purified from infected patients. While the extracellular traps should be completely disintegrated by a healthy person’s serum, the purified anti-NET antibodies significantly slowed the process.

“We knew that people with severe forms of Covid have higher amounts of these neutrophil extracellular traps, which amplify inflammation and promote blood clot formation,” said Jason Knight, Associate Professor of rheumatology at Michigan Medicine.

“We’ve now found that this process is exacerbated by the anti-NET antibodies, which disrupt our body’s immune homeostasis during Covid-19 infection,” Knight said.

However, it is unclear how Covid-19 induces the production of a wide range of autoantibodies, including anti-NETs.

Zuo believes that further research into the virus’s autoimmune aspects will not only lead to a better understanding of the disease, but will also shed light on the origins of autoimmune diseases.

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