Lars Jørgen Østergaard

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Richard T Davey, Unknown
  • Ruth Lynfield
  • ,
  • Dominic E Dwyer
  • ,
  • Marcello H Losso
  • ,
  • Alessandro Cozzi-Lepri
  • ,
  • Deborah Wentworth
  • ,
  • H Clifford Lane
  • ,
  • Robin Dewar, Unknown
  • Adam Rupert, Unknown
  • Julia A Metcalf, Unknown
  • Sarah L Pett, Unknown
  • Timothy M Uyeki
  • ,
  • Jose Maria Bruguera, Unknown
  • Brian Angus
  • ,
  • Nathan Cummins, Unknown
  • Jens Lundgren
  • ,
  • James D Neaton
  • ,
  • INSIGHT FLU 002 & 003 Study Groups (Lars Østergaard, member)

BACKGROUND: Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies.

METHODS: Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified.

RESULTS: In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only.

CONCLUSIONS: In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome.

Original languageEnglish
JournalPLOS ONE
Volume8
Issue2
Pages (from-to)e57121
ISSN1932-6203
DOIs
Publication statusPublished - 2013

    Research areas

  • Adult, Biological Markers, Cohort Studies, Cytokines, Disease Progression, Female, Humans, Inflammation Mediators, Influenza A Virus, H1N1 Subtype, Influenza, Human, Male, Middle Aged, Odds Ratio, Prognosis, Young Adult

See relations at Aarhus University Citationformats

ID: 84790419