Neutrophils and Neutrophil Extracellular Traps Drive Necroinflammation in COVID-19

Cells. 2020 Jun 2;9(6):1383. doi: 10.3390/cells9061383.

Abstract

The COVID-19 pandemic is progressing worldwide with an alarming death toll. There is an urgent need for novel therapeutic strategies to combat potentially fatal complications. Distinctive clinical features of severe COVID-19 include acute respiratory distress syndrome, neutrophilia, and cytokine storm, along with severe inflammatory response syndrome or sepsis. Here, we propose the putative role of enhanced neutrophil infiltration and the release of neutrophil extracellular traps, complement activation and vascular thrombosis during necroinflammation in COVID-19. Furthermore, we discuss how neutrophilic inflammation contributes to the higher mortality of COVID-19 in patients with underlying co-morbidities such as diabetes and cardiovascular diseases. This perspective highlights neutrophils as a putative target for the immunopathologic complications of severely ill COVID-19 patients. Development of the novel therapeutic strategies targeting neutrophils may help reduce the overall disease fatality rate of COVID-19.

Keywords: MERS-CoV; NETs; SARS-CoV-2; complement; coronavirus; necroinflammation; neutrophils; thrombosis.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / physiology
  • COVID-19
  • Cardiovascular Diseases / complications
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology*
  • Diabetes Complications / virology
  • Extracellular Traps / immunology*
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Necrosis / immunology
  • Necrosis / pathology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology*
  • SARS-CoV-2

Substances

  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2