Excessive lung release of neutrophil DNA traps may explain severe complications in Covid-19 patients

A multidisciplinary team of researchers from GIGA (ULiège) has detected significant amounts of DNA traps in distinct compartments of the lungs of patients who died from Covid-19. These traps, called NETs, 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.

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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 Covid-19. These traps, called NETs, 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 defence. 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 through DNA traps called Neutrophil Extracellular Traps or NETs. When massively released in certain compartments of the lungs, they 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 histo-pathological 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.

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Source

‘Neutrophil extracellular traps infiltrate the lung airway, interstitial and vascular compartments in severe Covid-19’, The Journal of Experimental Medicine, DOI 10.1084/jem.20201012

Auteurs

Coraline Radermecker ^1,2, Nancy Detrembleur ^3,4, Julien Guiot ^5,6, Etienne Cavalier ⁷, Monique Henket ^5,6, Céline d’Emal ⁸, Céline Vanwinge ⁹, Didier Cataldo ⁹, Cécile Oury ^8,5, Philippe Delvenne ^3,4,5, Thomas Marichal ^1,2,10

Prs Cécile Oury, Philippe Delvenne and Thomas Marichal contributed equally to the work

1. Laboratory of Immunophysiology, GIGA Institute, Liege University
2. Faculty of Veterinary Medicine, Liege University
3. Department of Pathology, CHU University Hospital, Liege University
4. Laboratory of Experimental Pathology, GIGA Institute, Liege University
5. Pneumology department, CHU Liège, GIGA Institute, Liege University
6. Laboratory of Pneumology, GIGA Institute, Liege University, 4000 Liege, Belgium.
7. Medical Chemistry, CIRM Institute, Liege University
8. Laboratory of Cardiology, GIGA Institute, Liege University
9. Laboratory of Tumor and Development Biology, GIGA Institute, Liege University
10. WELBIO, Walloon Excellence in Life Sciences and Biotechnology

Illustration

Neutrophil Extracellular traps (NETs), colorés en rose et vert, dans le poumon d’un patient ayant succombé à la Covid-19.

Press Contacts

Prof. Thomas Marichal, Welbio and ERC Investigator / Head of the Laboratory of Immunophysiology, GIGA-I³ Unit, University of Liège
+32 499  73 70 20 / t.marichal@uliege.be

Prof. Cécile Oury, Research Director Fund for Scientific Research F.R.S-FNRS / Head of the Cardiology Laboratory, GIGA-Cardiovascular Unit, University of Liège / President of the Belgian Society of Thrombosis and Haemostasis (BSTH)
+32 4 366 24 87 / cecile.oury@uliege.be

Prof. Philippe Delvenne, Head of Pathological Anatomy Laboratory of the CHU of Liège, Director of the Laboratory of Experimental Pathology, University of Liège
+32 4 366 24 11 / p.delvenne@uliege.be

Dr. Coraline Radermecker, Postdoctoral Research for the Fund for Scientific Research – FNRS at the Laboratory of Immunophysiology, GIGA-I³ Unit, University of Liège
+32 4 366 36 71 / C.Radermecker@uliege.be