Metabolite profiles associated with disease progression in influenza infection

Chris H Wendt, Sandra Castro-Pearson, Jennifer Proper, Sarah Pett, Timothy J Griffin, Virginia Kan, Javier Carbone, Nikolaos Koulouris, Cavan Reilly, James D Neaton, INSIGHT FLU003 Plus Study Group, Chris H Wendt, Sandra Castro-Pearson, Jennifer Proper, Sarah Pett, Timothy J Griffin, Virginia Kan, Javier Carbone, Nikolaos Koulouris, Cavan Reilly, James D Neaton, INSIGHT FLU003 Plus Study Group

Abstract

Background: We performed metabolomic profiling to identify metabolites that correlate with disease progression and death.

Methods: We performed a study of adults hospitalized with Influenza A(H1N1)pdm09. Cases (n = 32) were defined by a composite outcome of death or transfer to the intensive care unit during the 60-day follow-up period. Controls (n = 64) were survivors who did not require transfer to the ICU. Four hundred and eight metabolites from eight families were measured on plasma sample at enrollment using a mass spectrometry based Biocrates platform. Conditional logistic regression was used to summarize the association of the individual metabolites and families with the composite outcome and its major two components.

Results: The ten metabolites with the strongest association with disease progression belonged to five different metabolite families with sphingolipids being the most common. The acylcarnitines, glycerides, sphingolipids and biogenic metabolite families had the largest odds ratios based on the composite endpoint. The tryptophan odds ratio for the composite is largely associated with death (OR 17.33: 95% CI, 1.60-187.76).

Conclusions: Individuals that develop disease progression when infected with Influenza H1N1 have a metabolite signature that differs from survivors. Low levels of tryptophan had a strong association with death.

Registry: ClinicalTrials.gov Identifier: NCT01056185.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: The views expressed in this article are those of the authors and do not reflect the views of the US Government, the National Institutes of Health, the Department of Veterans Affairs, the funders, or any of the authors’ affiliated academic institutions. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Log odds ratios comparing the…
Fig 1. Log odds ratios comparing the upper vs. lower tertile after adjusting for duration of symptoms and matching factors by metabolite family.
Referenced: Ten strongest odd ratios as well as Kynurenine and Tryptophan.

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