Summary: Patients with severe COVID-19 infections have higher blood levels of neutrophil extracellular traps (NETs), which produce NETosis, an inflammatory type of neutrophil cell death. Researchers believe the NETs may be relevant to numerous aspects of novel coronavirus as thrombosis and inflammation are hallmarks of the severe infection.
Source: University of Michigan
New research finds a connection between destructive white blood cells and a more severe disease course in patients with COVID-19.
“We found that patients with COVID-19 infection have higher blood levels of neutrophil extracellular traps, also called NETs, which are a product of an inflammatory type of neutrophil cell death called NETosis,” says first author Yu (Ray) Zuo, M.D., a Michigan Medicine rheumatologist.
Zuo worked on the study with Yogen Kanthi, M.D., a cardiologist and vascular medicine specialist at the Michigan Medicine Frankel Cardiovascular Center, and Jason Knight, M.D., Ph.D., a rheumatologist at Michigan Medicine, who study inflammation and neutrophils. The researchers analyzed blood samples from 50 patients with COVID-19 for this publication.
Zuo and colleagues say, in light of the COVID-19 pandemic, there is an urgent need to better understand what causes the inflammatory storm and blood clots triggered by SARS-CoV-2 infection—a storm that leads to respiratory failure and a requirement for mechanical ventilation in many patients. They believe NETs may be relevant to many aspects of COVID-19 research, given that thrombosis and inflammation are hallmarks of severe infection.
This is the first publication to come out of the Frankel CVC’s CV Impact Research Ignitor Grant program, which was created to address COVID-19 from both basic science and clinical perspectives.
About this neuroscience research article
Source: University of Michigan Media Contacts: Haley Otman – University of Michigan Image Source: The image is credited to Stephanie King.
In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis — including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n = 50 patients, n = 84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.