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Antiviral metabolite 3'-Deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19

Mehta, Ravi; Chekmeneva, Elena; Jackson, Heather; Sands, Caroline; Mills, Ewurabena; Arancon, Dominique; Li, Ho Kwong; ... Sriskandan, Shiranee; + view all (2022) Antiviral metabolite 3'-Deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19. Med 10.1016/j.medj.2022.01.009. Green open access

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Abstract

Background: There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing. Methods: Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with viral infections including COVID-19, bacterial infections, inflammatory conditions, and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings. Associations between whole-blood gene expression and the identified metabolite of interest were examined. Findings: 3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), was detected for the first time in serum. When comparing 60 viral to 101 non-viral cases in the discovery cohort, ddhC was the most differentially abundant metabolite, generating an area under the receiver operating characteristic curve (AUC) of 0.954 (95% CI: 0.923-0.986). In the validation cohort, ddhC was again the most significantly differentially abundant metabolite when comparing 40 viral to 40 bacterial cases, generating an AUC of 0.81 (95% CI 0.708-0.915). Transcripts of viperin and CMPK2, enzymes responsible for ddhCTP synthesis, were amongst the five genes most highly correlated to ddhC abundance. Conclusions: The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and CMPK2 are implicated in ddhC production in vivo. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness, and acute infection management.

Type: Article
Title: Antiviral metabolite 3'-Deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.medj.2022.01.009
Publisher version: https://doi.org/10.1016/j.medj.2022.01.009
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: COVID-19, antiviral, bacterial, biomarker, ddhC, mass spectrometry, metabolomics, serum, viral
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10143774
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