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.
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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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