Virulence (Dec 2023)

Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19

  • Runa Kuley,
  • Bhargavi Duvvuri,
  • Jeffrey J. Wallin,
  • Nam Bui,
  • Mary Vic Adona,
  • Nicholas G. O’Connor,
  • Sharon K. Sahi,
  • Ian B. Stanaway,
  • Mark M. Wurfel,
  • Eric D. Morrell,
  • W. Conrad Liles,
  • Pavan K. Bhatraju,
  • Christian Lood

DOI
https://doi.org/10.1080/21505594.2023.2218077
Journal volume & issue
Vol. 14, no. 1

Abstract

Read online

ABSTRACTNeutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19. Elevated levels of calprotectin, neutrophil extracellular traps (NETs) and fMet were observed in COVID-19 patients (n = 68), particularly in critically ill patients, as compared to HC (n = 19, p < 0.0001). Of note, the levels of NETs were higher in ICU patients with COVID-19 than in ICU patients without COVID-19 (p < 0.05), suggesting a prominent contribution of NETs in COVID-19. Additionally, plasma from COVID-19 patients with mild and moderate/severe symptoms induced in vitro neutrophil activation through fMet/FPR1 (formyl peptide receptor-1) dependent mechanisms (p < 0.0001). fMet levels correlated with calprotectin levels validating fMet-mediated neutrophil activation in COVID-19 patients (r = 0.60, p = 0.0007). Our data indicate that fMet is an important factor contributing to neutrophil activation in COVID-19 disease and may represent a potential target for therapeutic intervention.

Keywords