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Elastase and Exacerbation of Neutrophil Innate Immunity are Involved in Multi-Visceral Manifestations of COVID-19
  • +11
  • Jean Louis Gueant,
  • Rosa Maria Rodriguez-Gueant,
  • Julien Fromonot,
  • Abderrahim OUSSALAH,
  • Huguette Louis,
  • Céline Chery,
  • Mickael Gette,
  • Stanislas Gleye,
  • Jonas Callet,
  • Jeremie Raso,
  • François Blanchecotte,
  • Patrick Lacolley,
  • Regis Guieu,
  • Veronique Regnault
Jean Louis Gueant
University of Lorraine
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Rosa Maria Rodriguez-Gueant
University of Lorraine
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Julien Fromonot
Université de la Méditerranée Faculté de Médecine Secteur Centre
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Abderrahim OUSSALAH
University of Lorraine
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Huguette Louis
University of Lorraine
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Céline Chery
University of Lorraine
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Mickael Gette
Université de la Méditerranée Faculté de Médecine Secteur Centre
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Stanislas Gleye
University of Lorraine
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Jonas Callet
University of Lorraine
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Jeremie Raso
University of Lorraine
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François Blanchecotte
Medical analysis laboratory L'ABO+, Chambray-les-Tours
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Patrick Lacolley
University of Lorraine
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Regis Guieu
Université de la Méditerranée Faculté de Médecine Secteur Centre
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Veronique Regnault
University of Lorraine
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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 (ambulatory subjects), local hospitals, and two regional university hospitals. The case 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 decreased by 10-fold, compared to 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 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 IL8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease of 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.

Peer review status:Published

01 Oct 2020Submitted to Allergy
03 Oct 2020Submission Checks Completed
03 Oct 2020Assigned to Editor
06 Oct 2020Reviewer(s) Assigned
18 Oct 2020Review(s) Completed, Editorial Evaluation Pending
18 Oct 2020Editorial Decision: Revise Minor
24 Nov 20201st Revision Received
30 Nov 2020Assigned to Editor
30 Nov 2020Submission Checks Completed
03 Dec 2020Reviewer(s) Assigned
04 Dec 2020Review(s) Completed, Editorial Evaluation Pending
06 Dec 2020Editorial Decision: Revise Minor
09 Dec 20202nd Revision Received
10 Dec 2020Submission Checks Completed
10 Dec 2020Assigned to Editor
10 Dec 2020Reviewer(s) Assigned
11 Dec 2020Review(s) Completed, Editorial Evaluation Pending
20 Dec 2020Editorial Decision: Revise Minor
22 Dec 20203rd Revision Received
23 Dec 2020Assigned to Editor
23 Dec 2020Submission Checks Completed
23 Dec 2020Editorial Decision: Accept
27 Feb 2021Published in Allergy. 10.1111/all.14746