Antiviral metabolite 3 '-deoxy-3 ',4 '-didelydro-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, Arkell, Paul, Rawson, Timothy M ORCID: 0000-0002-2630-9722, Hammond, Robert
et al (show 8 more authors) (2022) Antiviral metabolite 3 '-deoxy-3 ',4 '-didelydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19. MED, 3 (3). 204-+.

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<h4>Background</h4>There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing.<h4>Methods</h4>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.<h4>Findings</h4>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 with 101 non-viral cases in the discovery cohort, ddhC was the most significantly 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 with 40 bacterial cases, generating an AUC of 0.81 (95% CI 0.708-0.915). Transcripts of viperin and <i>CMPK2</i>, enzymes responsible for ddhCTP synthesis, were among the five genes most highly correlated with ddhC abundance.<h4>Conclusions</h4>The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and <i>CMPK2</i> are implicated in ddhC production <i>in vivo</i>. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness, and acute infection management.<h4>Funding</h4>NIHR Imperial BRC; UKRI.

Item Type: Article
Uncontrolled Keywords: Humans, Bacterial Infections, Virus Diseases, Cytidine, Antiviral Agents, COVID-19
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Mar 2023 08:31
Last Modified: 28 Mar 2023 08:31
DOI: 10.1016/j.medj.2022.01.009
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