Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies

Ruth Lynfield; Richard Davey; Dominic E Dwyer; Marcelo H Losso; Deborah Wentworth; Alessandro Cozzi-Lepri; Kathy Herman-Lamin; Grazyna Cholewinska; Daniel David; Stefan Kuetter; Zelalem Ternesgen; Timothy M Uyeki; H Clifford Lane; Jens Lundgren; James D Neaton; INSIGHT Influenza Study Group

doi:10.1371/journal.pone.0101785

Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies

Ruth Lynfield, Richard Davey, Dominic E Dwyer, Marcelo H Losso, Deborah Wentworth, Alessandro Cozzi-Lepri, Kathy Herman-Lamin, Grazyna Cholewinska, Daniel David, Stefan Kuetter, Zelalem Ternesgen, Timothy M Uyeki, H Clifford Lane, Jens Lundgren, James D Neaton, INSIGHT Influenza Study Group

Department of Clinical Medicine

26 Citations (Scopus)

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.

METHODS AND FINDINGS: 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.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.

Original language	English
Article number	e101785
Journal	PLOS ONE
Volume	9
Issue number	7
Pages (from-to)	1-15
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0101785
Publication status	Published - 8 Jul 2014

Keywords

Adult
Cohort Studies
Comorbidity
Disease Progression
Female
Follow-Up Studies
Hospitalization
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Male
Middle Aged
Mortality
Patient Outcome Assessment
Risk Factors
Severity of Illness Index
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0101785

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Lynfield, R., Davey, R., Dwyer, D. E., Losso, M. H., Wentworth, D., Cozzi-Lepri, A., Herman-Lamin, K., Cholewinska, G., David, D., Kuetter, S., Ternesgen, Z., Uyeki, T. M., Lane, H. C., Lundgren, J., Neaton, J. D., & INSIGHT Influenza Study Group (2014). Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies. PLOS ONE, 9(7), 1-15. [e101785]. https://doi.org/10.1371/journal.pone.0101785

Lynfield, R, Davey, R, Dwyer, DE, Losso, MH, Wentworth, D, Cozzi-Lepri, A, Herman-Lamin, K, Cholewinska, G, David, D, Kuetter, S, Ternesgen, Z, Uyeki, TM, Lane, HC, Lundgren, J, Neaton, JD & INSIGHT Influenza Study Group 2014, 'Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies', PLOS ONE, vol. 9, no. 7, e101785, pp. 1-15. https://doi.org/10.1371/journal.pone.0101785

@article{55a6b912d2d7470aa1035976a6ffd400,

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.METHODS AND FINDINGS: 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.",

keywords = "Adult, Cohort Studies, Comorbidity, Disease Progression, Female, Follow-Up Studies, Hospitalization, Humans, Influenza A Virus, H1N1 Subtype, Influenza, Human, Male, Middle Aged, Mortality, Patient Outcome Assessment, Risk Factors, Severity of Illness Index, Young Adult",

author = "Ruth Lynfield and Richard Davey and Dwyer, {Dominic E} and Losso, {Marcelo H} and Deborah Wentworth and Alessandro Cozzi-Lepri and Kathy Herman-Lamin and Grazyna Cholewinska and Daniel David and Stefan Kuetter and Zelalem Ternesgen and Uyeki, {Timothy M} and Lane, {H Clifford} and Jens Lundgren and Neaton, {James D} and {INSIGHT Influenza Study Group}",

year = "2014",

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doi = "10.1371/journal.pone.0101785",

language = "English",

volume = "9",

pages = "1--15",

journal = "PLoS Computational Biology",

issn = "1932-6203",

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TY - JOUR

T1 - Outcomes of influenza A(H1N1)pdm09 virus infection

T2 - results from two international cohort studies

AU - Lynfield, Ruth

AU - Davey, Richard

AU - Dwyer, Dominic E

AU - Losso, Marcelo H

AU - Wentworth, Deborah

AU - Cozzi-Lepri, Alessandro

AU - Herman-Lamin, Kathy

AU - Cholewinska, Grazyna

AU - David, Daniel

AU - Kuetter, Stefan

AU - Ternesgen, Zelalem

AU - Uyeki, Timothy M

AU - Lane, H Clifford

AU - Lundgren, Jens

AU - Neaton, James D

AU - INSIGHT Influenza Study Group

PY - 2014/7/8

Y1 - 2014/7/8

N2 - 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.METHODS AND FINDINGS: 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.

AB - 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.METHODS AND FINDINGS: 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.TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002--NCT01056354, FLU 003--NCT01056185.

KW - Adult

KW - Cohort Studies

KW - Comorbidity

KW - Disease Progression

KW - Female

KW - Follow-Up Studies

KW - Hospitalization

KW - Humans

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza, Human

KW - Male

KW - Middle Aged

KW - Mortality

KW - Patient Outcome Assessment

KW - Risk Factors

KW - Severity of Illness Index

KW - Young Adult

U2 - 10.1371/journal.pone.0101785

DO - 10.1371/journal.pone.0101785

M3 - Journal article

C2 - 25004134

SN - 1932-6203

VL - 9

SP - 1

EP - 15

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 7

M1 - e101785

ER -

Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies

Abstract

Keywords

UN SDGs

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