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

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, Robert Geffers, Jens Schreiber, Khyobeni Mozhui, Stephen Huang, Grant P. Parnell, Marek Nalos, Monika Holubova, Tracy Chew, David Booth, Anand Kumar, Anthony McLean and Klaus Schughart
Additional contact information
Benjamin M. Tang: Nepean Hospital
Maryam Shojaei: Nepean Hospital
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
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

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11249-y

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