Vitamin D – contrary to vitamin K – does not associate with clinical outcome in hospitalized COVID-19 patients

  1. Jona Walk
  2. Anton S.M. Dofferhoff
  3. Jody M.W. van den Ouweland
  4. Henny van Daal
  5. Rob Janssen

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Abstract

SARS-CoV-2 causes remarkably variable disease from asymptomatic individuals to respiratory insufficiency and coagulopathy. Vitamin K deficiency was recently found to associate with clinical outcome in a cohort of COVID-19 patients. Vitamin D has been hypothesized to reduce disease susceptibility by modulating inflammation, yet little is known about its role in disease severity. Considering the critical interaction between vitamin K and vitamin D in calcium and elastic fiber metabolism, we determined vitamin D status in the same cohort of 135 hospitalized COVID-19 patients by measuring blood 25(OH)D levels. We found no difference in vitamin D status between those with good and poor outcome (defined as intubation and/or death). Instead, we found vitamin D sufficient persons (25(OH)D >50 nmol/L) had accelerated elastic fiber degradation compared to those with mild deficiency (25(OH)D 25-50 nmol/L). Based on these findings, we hypothesize that vitamin D might have both favorable anti-inflammatory and unfavorable pro-calcification effects during COVID-19 and that vitamin K might compensate for the latter.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.07.20227512: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analyses were performed using GraphPad Prism 5 (version 5.03 for Windows).
    GraphPad Prism
    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:
    A limitation of the current study is that it was conducted in one region in a single month, while vitamin D levels are known to vary strongly between populations and throughout the year. As such it will be important to validate these results in other cohorts. Yet, there was significant variability in vitamin D status between our patients, which strengthens our findings. A small open-label pilot study recently suggested a decrease in ICU admissions after vitamin D administration [32], but larger controlled studies are needed to determine the role of supplementation in COVID-19. Regardless, considering the importance of vitamin K in protecting against the deleterious effects of calcium and the known interactions between vitamin D and vitamin K in calcium metabolism, it would be prudent to include investigation of vitamin K supplementation in any future clinical trial. Potential conflicts of interest: RJ discloses application of a patent on vitamin K in COVID-19. RJ, JW and ASMD have a scientific collaboration with Kappa Bioscience AS, a manufacturer of vitamin K2 (MK-7). JMWO and RJ are owners of Desmosine.com. HD declares no competing interests.

    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.

  2. Version published to 10.1101/2020.11.07.20227512v1 on medRxiv