Journal
ALLERGY
Volume 76, Issue 6, Pages 1846-1858Publisher
WILEY
DOI: 10.1111/all.14746
Keywords
COVID-19; DNase; innate immunity; myeloperoxidase; neutrophil extracellular traps (NETs)
Categories
Funding
- research project FHU ARRIMAGE
- French PIA project Lorraine Universite d'Excellence [ANR-15-IDEX-04-LUE]
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The study found that levels of neutrophil elastase and histone-DNA were significantly increased in COVID-19 patients, while DNase activity was notably decreased. These markers were associated with disease severity and multi-organ manifestations, suggesting they could potentially serve as biomarkers and therapeutic targets for severe systemic manifestations of COVID-19.
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.
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