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Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.
Tang, Benjamin M Shojaei, Maryam Teoh, Sally Meyers, Adrienne Ho, John Ball, T Blake Keynan, Yoav Pisipati, Amarnath Kumar, Aseem Eisen, Damon P
Tang, Benjamin M
Shojaei, Maryam
Teoh, Sally
Meyers, Adrienne
Ho, John
Ball, T Blake
Keynan, Yoav
Pisipati, Amarnath
Kumar, Aseem
Eisen, Damon P
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2019-07-31
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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.
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Nat Commun. 2019 Jul 31;10(1):3422. doi: 10.1038/s41467-019-11249-y.
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en
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2041-1723
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Attribution-NonCommercial-ShareAlike 4.0 International