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Nat Commun. 2019 Jul 31;10(1):3422. doi: 10.1038/s41467-019-11249-y.
Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.
Tang BM1,2,3, Shojaei M4,5, Teoh S4, Meyers A6, Ho J6, Ball TB6, Keynan Y7, Pisipati A8, Kumar A9, Eisen DP10, Lai K11, Gillett M12, Santram R13, Geffers R14, Schreiber J15, Mozhui K16, Huang S4, Parnell GP5, Nalos M4,17, Holubova M18, Chew T19, Booth D5, Kumar A20, McLean A4, Schughart K21,22,23.
Author information
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.
PMID: 31366921 DOI: 10.1038/s41467-019-11249-y
Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.
Tang BM1,2,3, Shojaei M4,5, Teoh S4, Meyers A6, Ho J6, Ball TB6, Keynan Y7, Pisipati A8, Kumar A9, Eisen DP10, Lai K11, Gillett M12, Santram R13, Geffers R14, Schreiber J15, Mozhui K16, Huang S4, Parnell GP5, Nalos M4,17, Holubova M18, Chew T19, Booth D5, Kumar A20, McLean A4, Schughart K21,22,23.
Author information
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.
PMID: 31366921 DOI: 10.1038/s41467-019-11249-y