Elastase and exacerbation of neutrophil innate immunity are involved in multi-visceral manifestations of COVID-19.

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.

• Authors: Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez, Julien Fromonot, Abderrahim Oussalah, Huguette Louis, Celine Chery, Mickael Gette, Stanislas Gleye, Jonas Callet, Jeremie Raso, François Blanchecotte, Patrick Lacolley, Régis Guieu, Véronique Regnault
• Journal: Allergy (Allergy) Vol. 76 Issue 6 Pg. 1846-1858 (06 2021) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 33484168 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Chemical References

• Histones

Topics

• COVID-19
• Extracellular Traps
• Histones
• Humans
• Immunity, Innate
• Neutrophils
• SARS-CoV-2