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Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis

BMJ 2013; 347 doi: (Published 23 August 2013) Cite this as: BMJ 2013;347:f5061
  1. Dominik Mertz, assistant professor12,
  2. Tae Hyong Kim, researcher2,
  3. Jennie Johnstone, researcher2,
  4. Po-Po Lam, researcher34,
  5. Michelle Science, staff physician5,
  6. Stefan P Kuster, staff physician6,
  7. Shaza A Fadel, researcher4,
  8. Dat Tran, assistant professor5,
  9. Eduardo Fernandez, researcher2,
  10. Neera Bhatnagar, librarian7,
  11. Mark Loeb, professor289
  1. 1Department of Medicine, McMaster University, Hamilton, ON, Canada
  2. 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton
  3. 3Mount Sinai Hospital, Toronto, ON, Canada
  4. 4Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto
  5. 5Department of Pediatrics, The Hospital for Sick Children, University of Toronto, ON, Canada
  6. 6University Hospital and University of Zurich, Zurich, Switzerland
  7. 7Health Sciences Library, McMaster University, Hamilton
  8. 8Department of Pathology and Molecular Medicine, McMaster University, Hamilton
  9. 9Michael G DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton
  1. Correspondence to: M Loeb Department of Pathology and Molecular Medicine, McMaster University MDCL 3203, 1200 Main St. W, Hamilton, ON, Canada L8N 3Z5 loebm{at}
  • Accepted 22 July 2013


Objective To evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza.

Design Systematic review.

Study selection Observational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes.

Data sources Medline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011.

Risk of bias assessment Newcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence.

Results 63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for “any risk factor” (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81).

Conclusion The level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.


  • We thank Stephen Walter for his comments and edits.

  • Contributors: All authors were involved in the conception and design of the study and the interpretation of data. DM and ML were responsible for the analysis and drafting of the article. All authors revised the manuscript critically for important intellectual content, gave final approval of the version to be published, had full access to all data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. DM and ML are guarantors.

  • Funding: This systematic review was funded by WHO as part of an ongoing process of reviewing and revising current WHO recommendations. The protocol for the review was discussed with WHO and its suggestions were incorporated into the protocol.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare that: DM was partly supported by a research scholarship from the Swiss National Science Foundation (PASMP3-132571) and the Lichtenstein-Stiftung and is a recipient of a research early career award from Hamilton Health Sciences Foundation (Jack Hirsh Fellowship); ML holds the Michael G DeGroote chair in infectious diseases at McMaster University; JJ receives salary support from the Canadian Institutes of Health Research; ML has been a paid consultant for GlaxoSmithKline, Novartis, and Sanofi Pasteur (vaccine manufacturers); all other authors have no relationships with companies that might have an interest in the submitted work in the previous three years; spouses, partners, or children of the authors have no financial relationship that may be relevant to the submitted work; all authors have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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