Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis

Maria Candida Cesta, Mara Zippoli, Carolina Marsiglia, Elizabeth M. Gavioli, Giada Cremonesi, Akram Khan, Flavio Mantelli, Marcello Allegretti, Robert Balk

Research output: Contribution to journalReview articlepeer-review


Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID-19 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS-CoV-2 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.

Original languageEnglish (US)
Article number2250010
JournalEuropean Journal of Immunology
Issue number1
StatePublished - Jan 2023


  • ARDS
  • COVID-19
  • CXCL8
  • immunomodulators

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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