Antiviral metabolite 3'-deoxy-3',4'-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19.
COVID-19
antiviral
bacterial
biomarker
ddhC
diagnostic
mass spectrometry
metabolomics
serum
viral
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
11 Mar 2022
11 Mar 2022
Historique:
received:
28
07
2021
revised:
14
11
2021
accepted:
21
01
2022
pubmed:
8
2
2022
medline:
8
2
2022
entrez:
7
2
2022
Statut:
ppublish
Résumé
There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing. 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. 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 The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and NIHR Imperial BRC; UKRI.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
CONCLUSIONS
The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and
FUNDING
BACKGROUND
NIHR Imperial BRC; UKRI.
Identifiants
pubmed: 35128501
doi: 10.1016/j.medj.2022.01.009
pii: S2666-6340(22)00044-7
pmc: PMC8801973
doi:
Substances chimiques
Antiviral Agents
0
Cytidine
5CSZ8459RP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
204-215.e6Subventions
Organisme : Medical Research Council
ID : MC_PC_12025
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206508/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R502376/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19040
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 207511/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 215214/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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