Longitudinal kinetics of the viral infection biomarker 3’-deoxy-3’,4’-didehydro-cytidine in SARS-CoV-2, influenza A virus and RSV human challenge models
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Author(s)
Type
Journal Article
Abstract
3’-deoxy-3’,4’-didehydro-cytidine (ddhC) is a recently discovered host biomarker for viral infections, though its temporal kinetics remain unclear. This study tests the hypothesis that ddhC is an acute phase reactant, rising shortly after viral infection and subsequently falling to baseline. We leveraged the precise monitoring facilitated by human challenge studies to investigate healthy participants inoculated with SARS-CoV-2, influenza A virus (H3N2), or respiratory syncytial virus (RSV). Using targeted liquid chromatography-tandem mass spectrometry, we quantified ddhC concentrations in serial plasma samples collected pre- and post-inoculation. In SARS-CoV-2 and H3N2 influenza A virus infection, but not RSV, ddhC levels peaked at 3-7 days post inoculation and declined to baseline by days 10-14. This pattern was also observed in asymptomatic or paucisymptomatic participants. A comparison of ddhC concentrations with matched timepoint whole blood gene expression revealed a correlation with interferon-related genes, including viperin and CMPK2 – enzymes implicated in its upstream biosynthesis. Our results suggest that ddhC is a biomarker of the acute phase of viral infection, with potential to guide early interventions to reduce antimicrobial resistance and strengthen pandemic preparedness. Future work should explore ddhC dynamics in natural and experimental infections across varying severities and assess its utility in diverse populations and healthcare settings.
Date Issued
2025-06-20
Date Acceptance
2025-05-25
Citation
npj Viruses, 2025, 3
ISSN
2948-1767
Publisher
Nature Research
Journal / Book Title
npj Viruses
Volume
3
Copyright Statement
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s44298-025-00132-x
Publication Status
Published
Article Number
50