Abstract Number: PB/CO08
Meeting: ISTH 2020 Congress
Background: While hyperinflammatory tissue-damaging, thromboembolic or immunothrombotic responses triggered by SARS-Cov-2 are thought to be major causes of respiratory failure and death in Covid-19, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can be formed in the lungs upon infection with respiratory viruses. They have the ability to promote lung damage, thrombosis and fibrosis, three cardinal features encountered in severe Covid-19. However, whether NETs infiltrate lungs from Covid-19 patients is unknown.
Aims: To assess whether NET structures could be identified in post-mortem lung biopsies from Covid-19 patients, and whether they located in particular lesions and micro-anatomical lung compartments.
Methods: We performed immunofluorescence staining of myeloperoxidase (MPO), citrullinated histone H3 (Cit-H3) and nuclear acid (DAPI) on sections of paraffin-embedded lung biopsies from four Covid-19 patients who succumbed Covid-19 and from four patients who died from a Covid-19-unrelated cause.
Results: The four patients represented prototypical severe and fatal cases of Covid-19, characterized by pneumonia and fatal respiratory distress associated with signs of systemic inflammation, neutrophilia and coagulopathy. NETs were uniquely detected in the lungs of each Covid-19 patients (Figure 1). In lungs from non-Covid-19 patients, we only sporadically detected MPO-positive ‘primed’ neutrophils, whose nuclei stained positive for Cit-H3. Detailed histopathological analysis revealed widely distributed NET-infiltrating areas encompassing several lung compartments, including arteriolar microthrombi, neutrophil-rich inflammatory areas of lung interstitium as well as alveoli or bronchioles where they often co-localized with occluding fibrin-rich deposits.
Conclusions: Our data support the hypothesis that NETs may represent drivers of Covid-19-associated severe pulmonary complications, and suggest that NET-targeting approaches could represent potential avenues for the treatment of uncontrolled tissue-damaging, thrombotic or fibrotic responses to SARS-Cov-2.
[NETs are uniquely detected in lungs of Covid-19 patients.]
To cite this abstract in AMA style:Oury C, Radermecker C, Detrembleur N, Guiot J, Henket M, D'Emal C, Vanwinge C, Cataldo D, Delvenne P, Marichal T. Neutrophil Extracellular Traps Infiltrate Lung Vascular, Interstitial and Airway Compartments in Severe Covid-19 [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/neutrophil-extracellular-traps-infiltrate-lung-vascular-interstitial-and-airway-compartments-in-severe-covid-19/. Accessed September 27, 2023.
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