Unravelling the debate on heme effects in COVID-19 infections

  1. Marie-Thérèse Hopp
  2. Daniel Domingo-Fernández
  3. Yojana Gadiya
  4. Milena S. Detzel
  5. Benjamin F. Schmalohr
  6. Francèl Steinbock
  7. Diana Imhof
  8. Martin Hofmann-Apitius

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Abstract

The SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 pathogenesis. Four COVID-19 related proteins, i.e. the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options.

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  1. Version published to 10.1101/2020.06.09.142125v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.06.09.142125: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Thus, homology models were built using YASARA version 19.12.14 and the hm_build macro with default settings (Krieger and Vriend, 2014).
    YASARA
    suggested: (YASARA, RRID:SCR_017591)
    We compiled the two KGs encoded in Biological Expression Language (BEL) using PyBEL (Hoyt et al., 2018) directly from their public repositories (i.e. https://github.com/covid19kg and https://github.com/hemekg/) and superimposed their interactions onto a merged network.
    PyBEL
    suggested: (PyBEL, RRID:SCR_017660)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, our approach is not without limitations as our analysis is restricted to a limited number of scientific articles. Furthermore, there is an unbalanced source of information when comparing the tremendous amount of literature that is currently being published on COVID-19 versus the information that is currently included in heme KG for heme. The findings described herein require a more detailed experimental investigation with dedicated experiments for each of the reported relations that shed light on the underlying biochemical mechanisms as well as for the full characterization of the heme-binding capacity of the proposed proteins. Nevertheless, the results of this study draw attention to a relationship that could be plausible based on the current characterization of COVID-19 by clinical parameters. A correlation between the symptoms of COVID-19 infection and the consequences of excess heme does not necessarily have to be related, but in specific cases it may correlate or even cause a more severe course of the disease in existing hemolytic conditions or hemolysis-provoking events.

    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.

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  3. Version published to 10.1101/2020.06.09.142125v1 on bioRxiv