New research has offered fresh insights into how blood clots form in some people with COVID-19. The US study suggests that the life-threatening blood clots and inflammation are driven by overactive neutrophils in the immune system.
The research was led by Drs Joshua Schiffman and Christian Con Yost of the University of Utah, with collaborators at PEEL Therapeutics, Cold Spring Harbour Laboratory and Weill Cornell Medicine.
They explain that ‘neutrophil extracellular traps’, or NETs, are produced by neutrophils to capture and destroy viruses and bacteria. But too many can accumulate during a persistent infection, and trigger immunothrombosis, leading to acute respiratory distress syndrome.
The researchers took a closer look at this process by comparing 33 COVID-19 patients with 17 healthy people matched for age and sex. They found that soluble and cellular factors which are known to trigger NETs were significantly increased in people with COVID-19, particularly in those with the most severe disease and those who would later die. Autopsies of the lung “confirmed NET-containing microthrombi with neutrophil-platelet infiltration”, the researchers write.
Lab tests also showed that plasma from COVID-19 patients triggered NET formation by neutrophils from healthy donors. “Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and may represent targets for therapeutic intervention,” they report.
The team also found that a molecule found in umbilical cord blood, neonatal NET-Inhibitory Factor (nNIF) blocked the formation of NETs in the lab. The study was reported last Monday (29th June) in the journal Blood.
Dr Mikala Egeblad, one of the researchers from Cold Spring Harbour Laboratory, said: “It will be important to investigate NETs role in thrombosis, not only in light of the COVID-19 pandemic, but also to understand their broader role in disease.
“Excess NETs are formed in other viral diseases. We also know that clotting is a major cause of death in people with end-stage cancer, so what we are learning in COVID-19 may help us understand basic properties in cancer and other diseases.”
Middleton EA, He XY, Denorme F, Campbell RA, Ng D, Salvatore SP, Mostyka M, Baxter-Stoltzfus A, Borczuk AC, Loda M, Cody MJ, Manne BK, Portier I, Harris E, Petrey AC, Beswick EJ, Caulin AF, Iovino A, Abegglen LM, Weyrich AS, Rondina MT, Egeblad M, Schiffman JD, Yost CC. (2020) “Neutrophil Extracellular Traps (NETs) Contribute to Immunothrombosis in COVID-19 Acute Respiratory Distress Syndrome.” Blood, doi: 10.1182/blood.2020007008
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