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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Med 2022 ; 3 (3): 204-215.e6 Nephropedia Template TP
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Antiviral metabolite 3 -deoxy-3 ,4 -didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19 #MMPMID35128501
Mehta R; Chekmeneva E; Jackson H; Sands C; Mills E; Arancon D; Li HK; Arkell P; Rawson TM; Hammond R; Amran M; Haber A; Cooke GS; Noursadeghi M; Kaforou M; Lewis MR; Takats Z; Sriskandan S
Med 2022[Mar]; 3 (3): 204-215.e6 PMID35128501show ga
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 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 CMPK2, enzymes responsible for ddhCTP synthesis, were among the five genes most highly correlated with 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. FUNDING: NIHR Imperial BRC; UKRI.