Excessive release of neutrophil DNA traps may drive lung pathology in severe COVID-19
Neutrophil extracellular traps (NETs), composed of DNA (blue), Cit-H3 (red), and MPO (green), in the lung of a patient who succumbed to COVID-19. Credit: © 2020 Radermecker et al. Originally published in Journal of Experimental Medicine. https://doi.org/10.1084/jem.20201012
A multidisciplinary team of researchers from the University of Liège (Belgium) has detected significant amounts of DNA traps in distinct compartments of the lungs of patients who died from severe COVID-19. These traps, called NETs, (neutrophil extracellular traps) are released massively into the airways, the lung tissue and the blood vessels. Such excessive release could be a major contributor to severe disease complications leading to in-hospital death. These results are published this week in the Journal of Experimental Medicine.
Neutrophils are innate immune cells that act as the immune system’s first line of defense. However, when over-activated, they can play a toxic role, as in the case of autoimmune diseases and chronic inflammatory diseases, for example. Neutrophils have the ability to release their own DNA, which in certain compartments of the lungs can cause toxic effects.
“Here, we have detected substantial quantities of NETs in distinct compartments of the lungs of patients who died from COVID-19 at the University Hospital (CHU) of Liège and who exhibited histopathological features of diffuse alveolar damage, whereas these DNA traps were absent in the lungs of patients who died from another cause,” explains Prof. Thomas Marichal, Welbio and ERC Investigator, head of the Immunophysiology Laboratory at the GIGA Institute of the University of Liège. The presence of NETs in the blood vessels, pulmonary interstitium, and airways could explain the formation of fibrin-rich clots underlying highly prevalent thrombotic events and different aspects of lung damage resulting from an uncontrolled activation of the immune system leading to the “cytokine storm”.
Also composed of Prof. Cécile Oury (Fund for Scientific Research – F.R.S.-FNRS, Head of the Cardiology Laboratory, GIGA, ULiège) and Prof. Philippe Delvenne (Head of Pathological Anatomy Laboratory of the CHU of Liège, Director of the Laboratory of Experimental Pathology, ULiège) and Dr. Coraline Radermecker (Postdoctoral Research for the Fund for Scientific Research – FNRS at the Laboratory of Immunophysiology, GIGA, ULiège), the research team was able to characterize the presence and precise localization of NETs in the lungs using imaging techniques associated with histopathological analyses.
“We are the first team in the world to identify the presence of NETs in several compartments of the lungs of patients with COVID-19,” explains Coraline Radermecker, first author of this study published in the Journal of Experimental Medicine.
“Clinical trials aimed at degrading these NETs in the hope of improving the condition of patients with advanced disease are being conducted by other teams around the world. Our study validates these therapeutic approaches by demonstrating that NETs are associated with the severe complications of COVID-19,” added Thomas Marichal.
“NET-targeting pharmacological approaches exist, with drugs already available, such as dornase alfa used in cystic fibrosis” explains Cécile Oury. As part of the prevention and treatment of thrombotic complications, she also stresses the need to implement current heparin-based recommendations. The fight against the excessive release of NETs appears to be a complementary route that could prove efficacy.
“We will now continue our research on the effects of COVID-19 on other organs, including the heart, another organ frequently affected in this disease, and further refine our knowledge of the mechanisms that lead to severe forms of the disease”, Thomas Marichal concludes.
Materials provided by the University of Liège. Content may be edited for clarity, style, and length.