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Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection

Author

Listed:
  • Benjamin M. Tang

    (Nepean Hospital
    The Westmead Institute for Medical Research
    Marie Bashir Institute for Infectious Diseases and Biosecurity)

  • Maryam Shojaei

    (Nepean Hospital
    The Westmead Institute for Medical Research)

  • Sally Teoh

    (Nepean Hospital)

  • Adrienne Meyers

    (University of Manitoba)

  • John Ho

    (University of Manitoba)

  • T. Blake Ball

    (University of Manitoba)

  • Yoav Keynan

    (University of Manitoba)

  • Amarnath Pisipati

    (Harvard University)

  • Aseem Kumar

    (Laurentian University)

  • Damon P. Eisen

    (Townsville Hospital)

  • Kevin Lai

    (Westmead Hospital)

  • Mark Gillett

    (Royal North Shore Hospital)

  • Rahul Santram

    (St. Vincent Hospital)

  • Robert Geffers

    (Helmholtz Centre for Infection Research)

  • Jens Schreiber

    (Otto-von-Guerike University of Magdeburg, Clinic of Pneumology)

  • Khyobeni Mozhui

    (University of Tennessee Health Science Centre)

  • Stephen Huang

    (Nepean Hospital)

  • Grant P. Parnell

    (The Westmead Institute for Medical Research)

  • Marek Nalos

    (Nepean Hospital
    Medical Faculty Plzen, Charles University Prague)

  • Monika Holubova

    (Medical Faculty Plzen, Charles University Prague)

  • Tracy Chew

    (The University of Sydney)

  • David Booth

    (The Westmead Institute for Medical Research)

  • Anand Kumar

    (University of Manitoba)

  • Anthony McLean

    (Nepean Hospital)

  • Klaus Schughart

    (Helmholtz Centre for Infection Research
    University of Veterinary Medicine
    University of Tennessee Health Science Centre)

Abstract

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817–0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.

Suggested Citation

  • Benjamin M. Tang & Maryam Shojaei & Sally Teoh & Adrienne Meyers & John Ho & T. Blake Ball & Yoav Keynan & Amarnath Pisipati & Aseem Kumar & Damon P. Eisen & Kevin Lai & Mark Gillett & Rahul Santram &, 2019. "Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11249-y
    DOI: 10.1038/s41467-019-11249-y
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