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

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.

SUBMITTER: Tang BM

PROVIDER: S-EPMC6668409 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Tang Benjamin M BM Shojaei Maryam M Teoh Sally S Meyers Adrienne A Ho John J Ball T Blake TB Keynan Yoav Y Pisipati Amarnath A Kumar Aseem A Eisen Damon P DP Lai Kevin K Gillett Mark M Santram Rahul R Geffers Robert R Schreiber Jens J Mozhui Khyobeni K Huang Stephen S Parnell Grant P GP Nalos Marek M Holubova Monika M Chew Tracy T Booth David D Kumar Anand A McLean Anthony A Schughart Klaus K

Nature communications 20190731 1

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 neutr ...[more]

PMID: 31366921

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Project description:BackgroundInfluenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China.MethodsWe conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza.ResultsDuring the study period, 15 354 children aged <15 years with signs and symptoms of SARI were enrolled at hospital admission. severe acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. P<.05). Only 16% (1116/7145) of enrolled patients had received seasonal trivalent influenza vaccination within 12 months of hospital admission. Non-vaccinated influenza cases were more likely than vaccinated influenza cases to have pneumonia (31/133, 23% vs 37/256, 15%, P<.05). severe acute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, P<.05).ConclusionsInfluenza A (H3N2) virus infection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children.

Dataset Information

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

Publications

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

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