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

Davey, Richard T., Jr., Lynfield, Ruth, Dwyer, Dominic E., Losso, Marcello H., Cozzi-Lepri, Alessandro, Wentworth, Deborah, Lane, H. Clifford, Dewar, Robin, Rupert, Adam, Metcalf, Julia A., Pett, Sarah L., Uyeki, Timothy M., Maria Bruguera, Jose, Angus, Brian, Cummins, Nathan, Lundgren, Jens, Neaton, James D., INSIGHT FLU 002 & 003 Study Groups and Emery, Sean (2013) The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies. PLoS One, 8 2: . doi:10.1371/journal.pone.0057121


Author Davey, Richard T., Jr.
Lynfield, Ruth
Dwyer, Dominic E.
Losso, Marcello H.
Cozzi-Lepri, Alessandro
Wentworth, Deborah
Lane, H. Clifford
Dewar, Robin
Rupert, Adam
Metcalf, Julia A.
Pett, Sarah L.
Uyeki, Timothy M.
Maria Bruguera, Jose
Angus, Brian
Cummins, Nathan
Lundgren, Jens
Neaton, James D.
INSIGHT FLU 002 & 003 Study Groups
Emery, Sean
Title The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-02-27
Sub-type Article (original research)
DOI 10.1371/journal.pone.0057121
Open Access Status DOI
Volume 8
Issue 2
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
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 3rd versus 1st 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 3rd versus 1st 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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