Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients

  1. Tiffany Thomas
  2. Davide Stefanoni
  3. Monika Dzieciatkowska
  4. Aaron Issaian
  5. Travis Nemkov
  6. Ryan C. Hill
  7. Richard O. Francis
  8. Krystalyn E. Hudson
  9. Paul W. Buehler
  10. James C. Zimring
  11. Eldad A. Hod
  12. Kirk C. Hansen
  13. Steven L. Spitalnik
  14. Angelo D’Alessandro

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Abstract

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  1. Version published to 10.1021/acs.jproteome.0c00606
  2. ScreenIT

    SciScore for 10.1101/2020.06.29.20142703: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Blood collection and processing: This observational study was conducted according to the Declaration of Helsinki, in accordance with good clinical practice guidelines, and approved by the Columbia University Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Pathway analyses were performed with DAVID software and Ingenuity Pathway Analysis.
    DAVID
    suggested: (DAVID, RRID:SCR_001881)
    Ingenuity Pathway Analysis
    suggested: (Ingenuity Pathway Analysis, RRID:SCR_008653)
    Graphs and statistical analyses were prepared with GraphPad Prism 8.0 (GraphPad Software, Inc, La Jolla, CA)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Graphs and statistical analyses were prepared with GraphPad Prism 8.0, GENE E, and MetaboAnalyst 4.0.25 Spearman’s correlations and related p-values were calculated with R Studio.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    MetaboAnalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Unfortunately, owing to logistical limitations, we could not directly measure RBC parameters directly related to gas transport physiology, a limitation that we will address in follow-up studies. It is not clear whether the alterations of the N-terminus of AE1 are driven by oxidant stress alone or by an enzymatic activity secondary to the infection (e.g., calcium-activated proteases). However, although SARS-CoV-2 encodes cleaving enzymes (e.g., papain-like proteases), comparing our proteomics data with this viral genome did not produce any positive identifications. This suggests that the virus does not penetrate RBCs or, if it does, its protein components are rapidly degraded and not resynthesized owing to the lack of organelles; alternatively, our approach may not be sensitive enough to detect trace viral proteins in the background of ∼250 million hemoglobin molecules per RBC.29 Modification and oxidation of the N-termini of AE1, ANK1, and SPTB were accompanied by altered acyl-carnitines, fatty acids (especially saturated short- and medium-chain fatty acids), and lipid metabolism (especially sphingolipids). The latter is interesting because signaling through the N-terminus of AE1 mechanistically cross-regulates with sphingolipids to promote hemoglobin oxygen off-loading in response to physiological (e.g., high-altitude) or pathological (e.g., sickle cell disease) hypoxia.15,30 This signature is consistent with impaired membrane lipid homeostasis, which is not attributable to ...

    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.

    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.

  3. Version published to 10.1101/2020.06.29.20142703v1 on medRxiv