1. Elastase and exacerbation of neutrophil innate immunity are involved in multi‐visceral manifestations of COVID‐19
- Author
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Mickael Gette, Jonas Callet, François Blanchecotte, Jérémie Raso, Véronique Regnault, Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez, Stanislas Gleye, Huguette Louis, Céline Chéry, Abderrahim Oussalah, Julien Fromonot, Régis Guieu, Patrick Lacolley, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Laboratoire d'Analyses Médicales L'Abo+, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), The study was funded by the research project FHU ARRIMAGE and the French PIA project 'Lorraine Université d’Excellence,' reference ANR-15-IDEX04-LUE., IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), Lucas, Nelly, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
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0301 basic medicine ,Exacerbation ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Neutrophils ,[SDV]Life Sciences [q-bio] ,Immunology ,Extracellular Traps ,Histones ,03 medical and health sciences ,DNase ,0302 clinical medicine ,COVID‐19 ,medicine ,Humans ,Immunology and Allergy ,CXC chemokine receptors ,innate immunity ,ComputingMilieux_MISCELLANEOUS ,Innate immune system ,Lung ,biology ,business.industry ,SARS-CoV-2 ,Elastase ,COVID-19 ,neutrophil extracellular traps (NETs) ,Neutrophil extracellular traps ,Immunity, Innate ,3. Good health ,myeloperoxidase ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Neutrophil elastase ,Myeloperoxidase ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Original Article ,business - Abstract
Background Many arguments suggest that neutrophils could play a prominent role in COVID‐19. However, the role of key components of neutrophil innate immunity in severe forms of COVID‐19 has deserved insufficient attention. We aimed to evaluate the involvement of neutrophil elastase, histone‐DNA, and DNases in systemic and multi‐organ manifestations of COVID‐19. Methods We performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center, local hospitals, and two regional university hospitals. The cases were evaluated according to clinical and biological markers of severity and multi‐organ manifestations and compared to 35 healthy controls. Results Blood neutrophil elastase, histone‐DNA, myeloperoxidase‐DNA, and free dsDNA were dramatically increased, and DNase activity was decreased by 10‐fold, compared with controls. Neutrophil elastase and histone‐DNA were associated with intensive care admission, body temperature, lung damage, and markers of cardiovascular outcomes, renal failure, and increased interleukin‐6 (IL‐6), IL‐8, and CXCR2. Neutrophil elastase was an independent predictor of the computed tomography score of COVID‐19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL‐8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease in blood DNase activity. Conclusion Our results point out the key role of neutrophil innate immunity exacerbation in COVID‐19. Neutrophil elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID‐19., Blood levels of neutrophil elastase and histone‐DNA are associated with severe and systemic and multi‐organ manifestations of COVID‐19. Increased blood concentrations of neutrophil elastase and neutrophil extracellular traps are related to exacerbation of neutrophil stimulation through activated IL‐8/CXCR2 pathway. Neutrophil elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID‐19.
- Published
- 2021
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