Vitamin D status: a U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers

  1. Sebastian T Lugg
  2. William R Mackay
  3. Aduragbemi A Faniyi
  4. Sian E Faustini
  5. Craig Webster
  6. Joanne E Duffy
  7. Martin Hewison
  8. Adrian M Shields
  9. Dhruv Parekh
  10. Alex G Richter
  11. Aaron Scott
  12. David R Thickett

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Abstract

There is increasing evidence that vitamin D (VD) deficiency may increase individuals’ risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between VD deficiency and sufficiency and COVID-19 seropositivity within healthcare workers.

Methods

The study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12 May to 22 May 2020, from the University Hospitals Birmingham National Health Service Foundation Trust. Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D 3 levels, age, body mass index (BMI), sex, ethnicity, job role and comorbidities. Participants were grouped into four VD categories: (1) Severe VD deficiency (VD<30 nmol/L); (2) VD deficiency (30 nmol/L ≤VD<50 nmol/L); (3) VD insufficiency (50 nmol/L ≤VD<75 nmol/L); (4) VD sufficiency (VD≥75 nmol/L).

Results

When VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified. This trend repeated when participants were split into subgroups of age, sex, ethnicity, BMI and comorbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups in the total population and between groups of men and women; black, Asian and minority ethnic (BAME) group; BMI<30 (kg/m 2 ); 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared with the other groups. A larger proportion of those within the BAME group (vs white ethnicity) were severely VD deficient (p < 0.00001). A larger proportion of the 0 comorbidity subgroup were VD deficient in comparison to the 1+ comorbidity subgroup (p=0.046).

Conclusions

Our study has shown a U-shaped relationship for COVID-19 seropositivity in UK healthcare workers. Further investigation is required to determine whether high VD levels can have a detrimental effect on susceptibility to COVID-19 infection. Future randomised clinical trials of VD supplementation could potentially identify ‘optimal’ VD levels, allowing for targeted therapeutic treatment for those at risk.

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  1. Version published to 10.1136/bmjresp-2022-001258
  2. ScreenIT

    SciScore for 10.1101/2021.10.11.21264835: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This was part of the COVID-19 convalescent immunity study (COCO) approved by London - Camden & Kings Cross Research Ethics Committee (20/HRA/1817).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 spike glycoprotein antibodies were measured using a combined IgG, IgA, IgM ELISA antibody with 98.3% (95% CI: 96.4-99.4%) specificity and 98.6% sensitivity (95% CI: 92.6-100%) (Product code MK654, The Binding Site (TBS), Birmingham) [11].
    Anti-SARS-CoV-2 spike glycoprotein
    suggested: None
    IgM ELISA
    suggested: None
    Software and Algorithms
    SentencesResources
    This was part of the COVID-19 convalescent immunity study (COCO) approved by London - Camden & Kings Cross Research Ethics Committee (20/HRA/1817).
    COCO
    suggested: (CoCo, RRID:SCR_010947)
    Data was analysed using IBM SPSS Statistics (version 27).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.10.11.21264835v1 on medRxiv