Severe Hospitalization-Requiring Viral Infection With Influenza or COVID-19: Metabolic Pathway Analysis
Kirstine K Rasmussen1, Wendy Bannister1, Theis Itenov2,3
1Centre of Excellence for Health, Immunity and Infections, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Open Forum Infectious Diseases
|June 25, 2026
Summary
Metabolic pathways, including tryptophan catabolism, are linked to severe outcomes in influenza and SARS-CoV-2 infections. These shared mechanisms may help predict disease progression and guide treatment.
Area of Science:
- * Infectious Disease Research
- * Metabolomics
- * Clinical Biochemistry
Background:
- * Influenza and SARS-CoV-2 can cause severe respiratory failure, with underlying metabolic pathways not fully understood.
- * Tryptophan catabolism has been implicated in disease progression and adverse outcomes in various illnesses.
- * The study investigates shared metabolic pathways between influenza and SARS-CoV-2, focusing on tryptophan catabolism.
Purpose of the Study:
- * To determine if the association between tryptophan catabolism and disease progression is common to both influenza and SARS-CoV-2 infections.
- * To explore other metabolic pathways potentially involved in severe outcomes of these viral infections.
- * To identify shared biological mechanisms for risk stratification and potential therapeutic interventions.
Main Methods:
- * Pooled data from 3 prospective studies of hospitalized adults with influenza or SARS-CoV-2.
- * Nested case-control design: Cases (disease progression within 28 days) matched 1:2 to non-progressors.
- * Analysis of plasma kynurenine, tryptophan, and kynurenine/tryptophan ratio; metabolic profiling using unsupervised clustering and pathway analysis.
Main Results:
- * Higher plasma kynurenine and kynurenine/tryptophan ratios were significantly associated with disease progression in 303 patients, irrespective of the pathogen.
- * Two distinct metabolite modules correlated with disease progression: one rich in tryptophan catabolism products and amino acids, the other in lipids and xenobiotics.
- * Odds ratios (log2 increase) for kynurenine and kynurenine/tryptophan ratio were 1.81 and 1.89, respectively.
Conclusions:
- * Metabolite groups associated with disease progression are shared between influenza and SARS-CoV-2, indicating common underlying biological mechanisms.
- * These shared mechanisms highlight potential targets for risk stratification of patients.
- * Findings suggest possibilities for developing disease-modifying treatments applicable to both viral infections.
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