title: Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies.
abstract: BACKGROUND
  Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.
  
  
  RESULTS
  Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1-3) and 6 days (IQR 4-10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4-7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5-26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons.
  
  
  CONCLUSIONS
  Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.
authors.affiliation: Infectious Disease Division, Minnesota Department of Health, St. Paul, Minnesota, United States of America.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lynfield
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Davey
authors.affiliation: Department of Virology, Centre for Infectious Diseases and Microbiology, Westmead Hospital and University of Sydney, Westmead, New South Wales, Australia.
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.affiliation: HIV Unit, Department of Medicine, Hospital José María Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Losso
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Wentworth
authors.affiliation: Research Department of Infection and Population Health, University College London, London, England, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Kathy
authors.initials: K
authors.lastname: Herman-Lamin
authors.affiliation: Hospital for Infectious Diseases, Warsaw, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Cholewinska
authors.affiliation: Hospital Rawson, Infectología, Cordoba, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: David
authors.affiliation: Marlow Medical Group, Marlow, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuetter
authors.affiliation: Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Zelalem
authors.initials: Z
authors.lastname: Ternesgen
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Uyeki
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital/Rigshospitalet & University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lundgren
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
mesh_terms: D000328:Adult; D015331:Cohort Studies; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000235:genetics; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D063868:Patient Outcome Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult