The Association between Serum Biomarkers and Disease Outcome in Influenza A(H1N1)pdm09 Virus Infection: Results of Two International Observational Cohort Studies

Richard T. Davey, Ruth Lynfield, Dominic E. Dwyer, Marcello H. Losso, Alessandro Cozzi-Lepri, Deborah Wentworth, H. Clifford Lane, Robin Dewar, Adam Rupert, Julia A. Metcalf, Sarah L. Pett, Timothy M. Uyeki, Jose Maria Bruguera, Brian Angus, Nathan W Cummins, Jens Lundgren, James D. Neaton

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere57121
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 27 2013

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H1N1 Subtype Influenza A Virus
Biomarkers
Virus Diseases
cohort studies
Viruses
Influenza A virus
influenza
Human Influenza
Observational Studies
Disease Progression
biomarkers
Cohort Studies
disease course
Serum
infection
Inpatients
Odds Ratio
odds ratio
Outpatients
Inflammation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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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.; 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.; Bruguera, Jose Maria; Angus, Brian; Cummins, Nathan W; Lundgren, Jens; Neaton, James D.

In: PLoS One, Vol. 8, No. 2, e57121, 27.02.2013.

Research output: Contribution to journalArticle

Davey, RT, Lynfield, R, Dwyer, DE, Losso, MH, Cozzi-Lepri, A, Wentworth, D, Lane, HC, Dewar, R, Rupert, A, Metcalf, JA, Pett, SL, Uyeki, TM, Bruguera, JM, Angus, B, Cummins, NW, Lundgren, J & Neaton, JD 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, vol. 8, no. 2, e57121. https://doi.org/10.1371/journal.pone.0057121
Davey, Richard T. ; 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. ; Bruguera, Jose Maria ; Angus, Brian ; Cummins, Nathan W ; Lundgren, Jens ; Neaton, James D. / The Association between Serum Biomarkers and Disease Outcome in Influenza A(H1N1)pdm09 Virus Infection : Results of Two International Observational Cohort Studies. In: PLoS One. 2013 ; Vol. 8, No. 2.
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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.",
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AU - Davey, Richard T.

AU - Lynfield, Ruth

AU - Dwyer, Dominic E.

AU - Losso, Marcello H.

AU - Cozzi-Lepri, Alessandro

AU - Wentworth, Deborah

AU - Lane, H. Clifford

AU - Dewar, Robin

AU - Rupert, Adam

AU - Metcalf, Julia A.

AU - Pett, Sarah L.

AU - Uyeki, Timothy M.

AU - Bruguera, Jose Maria

AU - Angus, Brian

AU - Cummins, Nathan W

AU - Lundgren, Jens

AU - Neaton, James D.

PY - 2013/2/27

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N2 - 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.

AB - 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.

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