Metabolic and Lipidomic Markers Differentiate COVID-19 From Non-Hospitalized and Other Intensive Care Patients

  1. Franziska Schmelter
  2. Bandik Föh
  3. Alvaro Mallagaray
  4. Johann Rahmöller
  5. Marc Ehlers
  6. Selina Lehrian
  7. Vera von Kopylow
  8. Inga Künsting
  9. Anne Sophie Lixenfeld
  10. Emily Martin
  11. Mohab Ragab
  12. Roza Meyer-Saraei
  13. Fabian Kreutzmann
  14. Ingo Eitel
  15. Stefan Taube
  16. Nadja Käding
  17. Eckard Jantzen
  18. Tobias Graf
  19. Christian Sina
  20. Ulrich L. Günther

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Abstract

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

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  1. Version published to 10.3389/fmolb.2021.737039
  2. ScreenIT

    SciScore for 10.1101/2021.01.13.21249645: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Study Participants: All participants provided written informed consent according to the declaration of Helsinki.
    IRB: ICU patients with either COVID-19 or CS were included within the LUERIC-study at the University Hospital of Schleswig-Holstein (Campus Lübeck) after evaluation and approval by the corresponding ethics committee (LUERIC-MICROBIOME Nr. 19-019 and 19-019 A, University of Luebeck).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 antibody-positive individuals and healthy controls did not show any symptoms of COVID-19 and were recruited within the ELISA-study framework as approved by the corresponding ethics committee (ELISA Nr. 20-150, University of Luebeck).
    Anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Specifically, pairwise correlations were generated using the corr function provided by the Matlab Statistics Toolbox using Spearman type ranked correlations.
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)
    Spearman correlation plots and Forest plots were both generated using Prism 8.4.3 (GraphPad Software, LLC).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04443673RecruitingGlycine Supplement for Severe COVID-19

    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.

    About SciScore

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  3. Version published to 10.1101/2021.01.13.21249645v1 on medRxiv