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

Date:
September 14, 2020
Source:
University of Liege
Summary:
Researchers have 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.



FULL STORY ==========================================================================
A multidisciplinary team of researchers from the University of Lie`ge
(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 Lie`ge 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
Lie`ge. 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. Ce'cile Oury (Fund for Scientific Research -- F.R.S.- FNRS, Head of the Cardiology Laboratory,
GIGA, ULie`ge) and Prof. Philippe Delvenne (Head of Pathological
Anatomy Laboratory of the CHU of Lie`ge, Director of the Laboratory of Experimental Pathology, ULie`ge) and Dr Coraline Radermecker (Postdoctoral Research for the Fund for Scientific Research -- FNRS at the Laboratory
of Immunophysiology, GIGA, ULie`ge), 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
Ce'cile 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.


========================================================================== Story Source: Materials provided by University_of_Liege. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Coraline Radermecker, Nancy Detrembleur, Julien Guiot, Etienne
Cavalier,
Monique Henket, Ce'line d'Emal, Ce'line Vanwinge, Didier Cataldo,
Ce'cile Oury, Philippe Delvenne, Thomas Marichal. Neutrophil
extracellular traps infiltrate the lung airway, interstitial, and
vascular compartments in severe COVID-19. Journal of Experimental
Medicine, 2020; 217 (12) DOI: 10.1084/jem.20201012 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200914114129.htm

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