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

Allergy. 2021 Jun;76(6):1846-1858. doi: 10.1111/all.14746. Epub 2021 Feb 27.


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.

Keywords: COVID-19; DNase; innate immunity; myeloperoxidase; neutrophil extracellular traps (NETs).

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Histones