The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19

  1. Kentaro Tojo
  2. Yoh Sugawara
  3. Yasufumi Oi
  4. Fumihiro Ogawa
  5. Takuma Higurashi
  6. Yukihiro Yoshimura
  7. Nobuyuki Miyata
  8. Hajime Hayami
  9. Yoshikazu Yamaguchi
  10. Yoko Ishikawa
  11. Ichiro Takeuchi
  12. Natsuo Tachikawa
  13. Takahisa Goto

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Abstract

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

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  1. Version published to 10.1038/s41598-021-92921-6
  2. ScreenIT

    SciScore for 10.1101/2021.02.19.21252061: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study protocol was reviewed and approved by the institutional review boards of YCUH (Yokohama City University Certified Institutional Review Board, approval number: B200700099) and YMCH (Yokohama Municipal Citizen’s Hospital Institutional Review Board, approval number: 20-09-04).
    Consent: The need for informed consent was waived by the institutional review boards because of the observational design of the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using Prism software (version 9.0; GraphPad Software, San Diego, CA, USA).
    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: We detected the following sentences addressing limitations in the study:
    This study has some limitations. First, although we performed multivariate analysis adjusting for age and sex, there might be other confounders in the association between serum iron levels and disease severity. Second, we could not obtain the patients’ serum iron levels before SARS-COV-2 infection, although it is possible that the iron status before the infection might affect the serum iron levels on admission and the disease severity.

    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

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  3. Version published to 10.1101/2021.02.19.21252061 on medRxiv