Premium
Elastase and exacerbation of neutrophil innate immunity are involved in multi‐visceral manifestations of COVID‐19
Author(s) -
Guéant JeanLouis,
GuéantRodriguez RosaMaria,
Fromonot Julien,
Oussalah Abderrahim,
Louis Huguette,
Chery Celine,
Gette Mickael,
Gleye Stanislas,
Callet Jonas,
Raso Jeremie,
Blanchecotte François,
Lacolley Patrick,
Guieu Régis,
Regnault Véronique
Publication year - 2021
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14746
Subject(s) - neutrophil extracellular traps , neutrophil elastase , innate immune system , exacerbation , immunology , medicine , elastase , myeloperoxidase , immunity , absolute neutrophil count , systemic inflammation , inflammation , biology , immune system , biochemistry , toxicity , neutropenia , enzyme
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.