A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery

Siyuan Ma; Eric Koplin; Meghan H. Shilts; Markus Voehler; Girish Rachakonda; Rubén Gil-Redondo; Seesandra V. Rajagopala; Judith Sabaté del Río; Teresa Botta-Orfila; Oriol Sibila; Mohammad Asad; Esha Sehanobish; Elina Jerschow; Elizabeth Phillips; Óscar Millet; Simon A. Mallal; Suman R. Das

doi:10.1016/j.isci.2026.115390

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A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery

Journal article

Open access

Peer reviewed

A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery

Siyuan Ma, Eric Koplin, Meghan H. Shilts, Markus Voehler, Girish Rachakonda, Rubén Gil-Redondo, Seesandra V. Rajagopala, Judith Sabaté del Río, Teresa Botta-Orfila, Oriol Sibila, …

iScience, Vol.29(4), p.115390

2026

DOI: https://doi.org/10.1016/j.isci.2026.115390

PMID: 41971988

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Abstract

Health sciences

Immunology

Medical specialty

Medicine

COVID-19 has individualized disease trajectories during both acute infection and long-term recovery (“long COVID”), highlighting the need for biomarkers for the disease’s heterogeneity. In this study, we introduce “metabo-time,” a quantitative metabolic signature derived from serum metabolites and lipoproteins measured via nuclear magnetic resonance (NMR) spectroscopy. Metabo-time was stablished across two longitudinal and demographically diverse cohorts and validated in independent populations. It captures patient-specific metabolic states throughout the disease course. Longitudinally, it is disrupted during acute infection and normalizes during recovery, mirroring systemic oxidative stress and immune response dynamics. Importantly, metabo-time outperforms actual recovery time in predicting patients’ individualized normalization of oxidative stress. At baseline, it distinguishes infection severity and is associated with transcriptional activity in the upper airway. These findings establish metabo-time as a robust marker for tracking COVID-19 heterogeneity and progression, with potential utility for stratifying patients and informing therapeutic strategies, particularly in the context of SARS-CoV-2 recovery.

Details

Title: A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery
Authors/Creators: Siyuan Ma - Vanderbilt University Medical Center
Eric Koplin - Vanderbilt University Medical Center
Meghan H. Shilts - Vanderbilt University Medical Center
Markus Voehler - Vanderbilt University
Girish Rachakonda - Meharry Medical College
Rubén Gil-Redondo - CIC bioGUNE
Seesandra V. Rajagopala - Vanderbilt University Medical Center
Judith Sabaté del Río - Biological Fluids Biobank, IDIBAPS-Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain
Teresa Botta-Orfila - Hospital Clínic de Barcelona
Oriol Sibila - Hospital Clínic de Barcelona
Mohammad Asad - Hospital Clínic de Barcelona
Esha Sehanobish - Albert Einstein College of Medicine
Elina Jerschow - Mayo Clinic
Elizabeth Phillips - Vanderbilt University Medical Center
Óscar Millet - CIC bioGUNE
Simon A. Mallal - Vanderbilt University Medical Center
Suman R. Das - Vanderbilt University Medical Center
Publication Details: iScience, Vol.29(4), p.115390
Publisher: Elsevier Inc
Identifiers: 991005884939707891
Murdoch Affiliation: Research and Innovation Office; Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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