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

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Abstract

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  1. SciScore for 10.1101/2021.07.23.21260740: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Ethical approval was obtained to take deferred consent from patients (or next of kin/nominated consultee) to retain blood samples, including serum and RNA specimens, as well as clinical data (Research Ethics Committee [REC] references 14/SC/0008 and 19/SC/0116).
    IRB: Ethical approval was obtained to take deferred consent from patients (or next of kin/nominated consultee) to retain blood samples, including serum and RNA specimens, as well as clinical data (Research Ethics Committee [REC] references 14/SC/0008 and 19/SC/0116).
    Sex as a biological variablenot detected.
    RandomizationTo facilitate multi-omic comparison, serum samples from BioAID patients were prioritised if whole blood RNA-Sequencing had already been undertaken as part of an earlier study, where samples had been selected from the BioAID database using a random number generator.
    Blindingnot detected.
    Power AnalysisN=24 samples in each of two comparator groups were required to achieve a power of >90% to identify an AUC of at least 0.8, at a significance level of 0.01.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    To facilitate multi-omic comparison, serum samples from BioAID patients were prioritised if whole blood RNA-Sequencing had already been undertaken as part of an earlier study, where samples had been selected from the BioAID database using a random number generator.
    BioAID
    suggested: None
    13 Sera from additional BioAID patients were selected randomly from within individual infection groups using a random number generator in Excel.
    Excel
    suggested: None
    Raw data were converted to the mzML open-source format and signals below an absolute intensity threshold of 100 counts were removed using the MSConvert tool in ProteoWizard 17 before data extraction using XCMS,18 outputting a matrix of measurements (peak integrals) organised row-wise into samples and column-wise into LC-MS “features”, each of which is described by its mass:charge (m/z) value and chromatographic retention time.
    ProteoWizard
    suggested: (ProteoWizard, RRID:SCR_012056)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study should be viewed in the context of its limitations. Firstly, in order to ensure diagnostic certainty, we only included the extremes of bacterial infection in the form of bacteraemia. Secondly, our cohort did not include fungal and protozoan infections. Thirdly, we only performed internal cross-validation, which will need further confirmation in an external cohort. We plan to address these limitations in future work to assess the performance of ddhC in new patient cohorts, including fungal and non-bacteraemic bacterial infections, as well as other infections seen outside of the UK. Fourthly, our cohort represents patients unwell enough to seek hospital attention – further work will be required to assess the role of ddhC in less unwell patients presenting to primary care and determine whether it is detectable in minimally invasive samples such as urine or saliva. In conclusion, using high-fidelity metabolic profiling of serum from patients attending hospital, we found that the antiviral molecule ddhC is present in human serum during viral infection and represents an accurate biomarker for a wide range of viral infections, including COVID-19. If shown to perform consistently in further validation work, this biomarker will have a crucial role in the diagnostic repertoire for infectious diseases.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.