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A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia

Grant P Parnell1*, Anthony S McLean1, David R Booth2, Nicola J Armstrong34, Marek Nalos1, Stephen J Huang1, Jan Manak5, Wilson Tang6, Oi-Yan Tam7, Stanley Chan8 and Benjamin M Tang1

Author Affiliations

1 Department of Intensive Care Medicine, University of Sydney, Nepean Hospital and Nepean Clinical School, Derby Street, Kingswood, 2747, Australia

2 Institute for Immunology and Allergy Research, Westmead Millennium Institute, Darcy Road, Westmead, 2145, Australia

3 Cancer Research Program, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, 2010, Australia

4 School of Mathematics and Statistics, University of New South Wales, Kensington, 2052, Australia

5 Department of Metabolic Care and Gerontology, Charles University Hospital, Sokolska 581, Hradec Králové, 500 00, Czech Republic

6 Intensive Care Unit, North District Hospital, 9 Po Kin Road, Sheung Shui, Hong Kong

7 Intensive Care Unit, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong Island, Hong Kong

8 Department of Anaesthesia and Intensive Care, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong

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Critical Care 2012, 16:R157  doi:10.1186/cc11477

Published: 16 August 2012



Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome.


Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore.


The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection.


The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.