An untargeted metabolomic approach to identify antiviral defense mechanisms in memory leukocytes secreting in vitro IgG anti-SARS-Cov-2

  1. Gevi Federica
  2. Fanelli Giuseppina
  3. Lelli Veronica
  4. Zarletti Gianpaolo
  5. Tiberi Massimo
  6. De Molfetta Veronica
  7. Scapigliati Giuseppe
  8. Timperio Anna Maria

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Abstract

Available knowledge shows that individuals infected by SARS-CoV-2 undergo an altered metabolic state in multiple organs. Metabolic activities are directly involved in modulating the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism relates with inflammatory responses. To better elucidate the underlying biochemistry of leukocytes response, we focused our analysis on the possible relationships between SARS-CoV-2 post-infection stages and distinct metabolic pathways. Indeed, in cultures of peripheral blood mononuclear cells (PBMC, n=48) obtained 60-90 days after infection and showing in vitro IgG antibody memory for spike-S1 antigen (n=19), we observed a significant altered metabolism of tryptophan and urea cycle pathways. This work for the first time identifies metabolic routes in cell metabolism possibly related to later stages of immune defense against SARS-Cov-2 infection, namely when circulating antibodies may be absent, but an antibody memory is present. The results suggest a reprogramming of leukocyte metabolism after viral pathogenesis through activation of specific amino acid pathways possibly related to protective immunity against SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.20.453042: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided informed written consent to participate in the research project, and the study was approved by the Regional Ethical Board in Ospedale L.
    IRB: All participants provided informed written consent to participate in the research project, and the study was approved by the Regional Ethical Board in Ospedale L.
    Sex as a biological variableSubjects Recruitment: 43 subjects (24 males and 19 females,dataset) of different ages (ranging from 30 to 81 years) undergoing SARS-Cov-2 serological analysis (Centro Polispecialistico Giovanni Paolo I, Viterbo, I) were enrolled in this study from October 2020 to March 2021.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Mass spectrometry chromatograms were created for peak alignment, matching and comparison of parent and fragment ions with tentative metabolite identification (within a 2-p.p.m. mass-deviation range between the observed and expected results against an imported KEGG database).
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    Fold change analysis was performed on the entire metabolomics data set using the MetaboAnalyst 5.0 software.
    MetaboAnalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)
    In order to analyze a correlation network of the compounds in shared pathways, MetScape, an app implemented in Java and integrated with Cytoscape (version 3.8.2), was used.
    MetScape
    suggested: ( Metscape , RRID:SCR_014687)
    Cytoscape
    suggested: (Cytoscape, RRID:SCR_003032)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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

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  2. Version published to 10.1101/2021.07.20.453042 on bioRxiv