COVID-19 patients who suffer life-threatening complications such as blood clots and inflammation also experience dysregulated NETosis.
The correlation between excess NETs and the severity of COVID-19 has been clarified by researchers at the University of Utah (U of U) Health, PEEL Therapeutics, Cold Spring Harbor Laboratory (CSHL), and Weill Cornell Medicine. These researchers also report that the NETs induced by COVID-19 may be blocked by neonatal NET-Inhibitory Factor (nNIF).
Detailed findings appeared June 29 in the journal Blood, in an article titled, “Neutrophil Extracellular Traps (NETs) Contribute to Immunothrombosis in COVID-19 Acute Respiratory Distress Syndrome.”
The article reported that blood samples were collected from 33 hospitalized patients, as well as autopsy tissue. The article also described how the blood and tissue samples were examined for biomarkers of NET formation, biomarkers such as plasma myeloperoxidase (MPO)-DNA complexes, platelet factor 4, RANTES, and selected cytokines.
What is NETosis?
NETosis is a cell death process that generates neutrophil extracellular traps (NETs), extracellular webs of DNA and toxins that capture and kill pathogens. However, NETs may interact with platelets and form microthrombi that contribute to acute respiratory distress syndrome.
“In this prospective cohort study, we demonstrate a robust correlation between NETs and severity of respiratory illness in COVID-19,” the article’s authors wrote. “We measure the highest levels of circulating NETs in COVID-19 patients with endotracheal intubation and report for the first time the infiltration of platelet co-localization with citrullinated histone H3 positive neutrophils likely undergoing NETosis in the pulmonary microthrombi of patients who died from COVID-19.”
“This study tells us about a potential mechanism for lung injury in COVID-19 that had not previously been recognized as a possible target for treatment,” said Elizabeth Middleton, MD, the study’s first author and a critical care specialist at U of U Health.
Although further studies will be required, the NET-inhibitory protein may block exaggerated NET formation in COVID-19 patients,” noted Yost, whose laboratory at the U of U Health discovered nNIF in 2016. Yost also indicated that larger studies need to be performed to determine whether NETs could become a biomarker for COVID-19 severity. “We think exaggerated NETs could be a cause of morbidity and mortality in COVID-19,” he suggested.