Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs

  1. Jie Chen
  2. Kaibo Mei
  3. Lixia Xie
  4. Ping Yuan
  5. Jianyong Ma
  6. Peng Yu
  7. Wengen Zhu
  8. Chunhua Zheng
  9. Xiao Liu

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Abstract

Background

The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear.

Methods

We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system.

Results

Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low.

Conclusions

Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

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  1. Version published to 10.1186/s12937-021-00744-y
  2. ScreenIT

    SciScore for 10.1101/2020.10.24.20218974: (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
    Literature Search and study Selection: Two authors independently searched several databases (PubMed, Embase, medRxiv) using the following two groups of keywords with no language restrictions: 2019-novel coronavirus, SARS-CoV-2, COVID-19, 2019-nCoV, and vitamin D.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    All statistical analyses were conducted by using Review Manager version 5.3 (The Cochrane Collaboration 2014; Nordic Cochrane Center Copenhagen, Denmark).
    Cochrane Collaboration
    suggested: None

    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:
    Study Limitations: The present meta-analysis has several limitations. There is high heterogeneity in our meta-analysis, which might derive from the study design and variability in baseline characteristics. For example, several studies have shown that the mortality rate for black patients is higher than the rate for white COVID-19 patients[26, 27]. Second, many factors can modulate vitamin D status, including genetic polymorphisms, age, health, sun exposure behavior, season, and so on[21]. Although we only included studies that performed multivariable analysis, some potential risk factors were not fully adjusted, which might also have affected our results. Therefore, further research might adjust for additional confounding factors.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04407286CompletedVitamin D Testing and Treatment for COVID 19
    NCT04482673RecruitingVitamin D Supplementation in the Prevention and Mitigation o…

    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 10.1101/2020.10.24.20218974v1 on medRxiv