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PLoS One. 2013;8(2):e57121. doi: 10.1371/journal.pone.0057121. Epub 2013 Feb 27.

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

Collaborators (228)

Munroe D, Rappoport C, Schwarze S, Aagaard B, Adzic D, Grarup J, Herrero P, Jansson P, Jakobsen ML, Jensen B, Jensen KB, Juncher H, Kjær J, Lundgren J, Lopez P, Mocroft A, Pearson M, Portas B, Sabin C, Tillmann K, Babiker A, Braimah N, Collaco-Moraes Y, Hudson F, Kummeling I, Pacciarini F, DuChene NP, George M, Harrison M, Herman K, Krum E, Larson G, Nelson R, Quan K, Quan SF, Reilly C, Schultz T, Thompson G, Wyman N, Avihingsanon A, Cassar L, Charoentonpuban K, Emery S, Laohajinda K, Jupimai T, Lanusse I, Moricz A, Otegui I, Ruxrungtham K, Robson R, Finley E, Gordin F, Sanchez A, Vjecha M, Baxter J, Brown S, Ghedin E, Halpin R, Hoover M, Baseler B, Metcalf JA, Cox N, Gubareva L, Hancock K, Katz J, Klimov A, Shaw M, Rubinson L, Barcan L, Corral JA, David DO, Laplume HE, Lasala MB, Lopardo GD, Losso MH, Lupo S, Warley E, Bloch M, Dwyer DE, Moore R, Pett SL, Roth N, MengSoo T, Vlahakis E, Burgmann H, Clumeck N, De Wit S, Florence E, Weckx J, Perez C, Wolff MJ, Gerstoft J, Lundgren JD, stergaard L, Zilmer K, Bogner JR, Brockmeyer NH, Faetkenheuer G, Klinker H, Plettenberg A, Rockstroh J, Stephan C, Antoniadou A, Koratzanis G, Koulouris N, Polixronopoulos V, Sambatakou H, Vasilopoulos N, Caplinskas S, Rosa AL, Mendo F, Salazar R, Valencia J, Knysz B, Antunes F, Doroana M, Padayatchi N, Dalmau D, Fernandez-Cruz E, Gatell JM, SanzSanz J, Soriano V, Chetchotisakd P, Ruxrungtham K, Suwanpimolkul G, Leen CL, Cohen C, Cohn DL, DeHovitz JA, El-Sadr W, Glesby M, Gordin FM, Hodder S, Markowitz N, Novak RM, Schooley R, Simon GL, Tedaldi EM, Timpone J, Uslan DZ, Wade BH, Barcan L, Corral JA, David DO, Laplume HE, Lasala MB, Lopardo GD, Losso MH, Warley E, Dwyer DE, Elliott J, Konecny P, McBride J, Pett SL, Burgmann H, Clumeck N, De Wit S, Jorens P, Wolff MJ, Wu TC, Gerstoft J, Mathiesen L, Nielsen H, Østergaard L, Pedersen SS, Bergmann F, Bogner JR, Brockmeyer NH, Faetkenheuer G, Klinker H, Rockstroh J, Stephan C, Antoniadou A, Koratzanis G, Koulouris N, Polixronopoulos V, Sambatakou H, Vasilopoulos N, Maagaard A, Mendo F, Salazar R, Bakowska E, Horban A, Padayatchi N, Dalmau D, Estrada V, Fernandez-Cruz E, Freud HK, Garrido RM, Gatell JM, Moreno JS, Pano-Pardo JR, SanzSanz J, Soriano V, Chetchotisakd P, Ruxrungtham K, Suwanpimolkul G, Angus BJ, Chadwick DR, Dockrell D, Leen CL, Newport M, Wilkins E, Anderson H 3rd, Baker JV, Cohn DL, DeHovitz JA, El-Sadr W, Freiberg MS, Gordin FM, Gulick R, Gurka D, Hodder S, Markowitz N, Novak RM, Paez A, Reboli A, Sands M, Schooley R, Simon GL, Temesgen Z, Timpone J, Uslan DZ, Wade BH, Kabeya K, Bakowska E, Horban A, Patil N.

Author information

  • 1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. rdavey@niaid.nih.gov

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 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.

PMID:
23468921
[PubMed - indexed for MEDLINE]
PMCID:
PMC3584122
Free PMC Article

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