New evidence for how blood clots form in people with severe COVID-19

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In a new study, researchers found new evidence that overactive neutrophils–a common type of circulating immune cell–may drive the life-threatening blood clots and inflammation that occur in some patients with COVID-19.

They found high levels of the sticky, pathogen-trapping webs produced by the cells were linked to the most severe cases of COVID-19.

The research was conducted by a team at Cold Spring Harbor Laboratory (CSHL) and elsewhere.

Neutrophil extracellular traps (NETs) are a type of defense that the immune system deploys against certain pathogens–webs of DNA and toxins that ensnare and destroy viruses and bacteria.

When too many of these NETs accumulate during persistent infection, they can lead to acute respiratory distress syndrome, which leads many patients with COVID-19 to require intensive care.

In the study, the team examined NETs suspected role in COVID-19, collecting blood samples from 33 hospitalized patients, as well as autopsy tissue.

They found that biomarkers of NET formation were more abundant in patients who required ventilation, and highest in the three study participants who eventually died from COVID-19.

When the team examined the lungs of the patients who died, they found tiny clots of tangled NETs and blood platelets known as microthrombi scattered through the tissue.

They say excess NETs are formed in other viral diseases.

In addition, clotting is a major cause of death in people with end-stage cancer, so what they are learning in COVID-19 may help us understand basic properties in cancer and other diseases.

In the laboratory, neutrophils from patients with COVID-19 churned out exceptionally high levels of NETs, and the researchers found healthy neutrophils behaved the same way when they were exposed to plasma from patients with the illness.

They could stop NET production, however, by exposing cells to neonatal NET-Inhibitory Factor (nNIF), an anti-inflammatory peptide from umbilical cord blood that protects newborn babies.

Several therapies for dismantling NETs or preventing their formation are currently under investigation. These include the nNIF peptide, which is in pre-clinical development by PEEL Therapeutics.

One author of the study is CSHL Associate Professor Mikala Egeblad.

The study is published in Blood.

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