An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank

  1. Xue Li
  2. Jos van Geffen
  3. Michiel van Weele
  4. Xiaomeng Zhang
  5. Yazhou He
  6. Xiangrui Meng
  7. Maria Timofeeva
  8. Harry Campbell
  9. Malcolm Dunlop
  10. Lina Zgaga
  11. Evropi Theodoratou

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55–1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55–0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42–0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66–0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.

Article activity feed

  1. Version published to 10.1038/s41598-021-97679-5
  2. ScreenIT

    SciScore for 10.1101/2020.08.18.20177691: (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

    No key resources detected.

    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:
    Our study has a number of strengths and limitations. Firstly, UK Biobank is a large prospective study, with rich information on a range of demographic, lifestyle and health-related risk factors. Vitamin D plasma measurements were conducted in a single central processing laboratory using the Diasorin immunoassay, albeit a blood sample was taken over a decade ago and is unlikely to be representative of participants’ vitamin D status at the time of the pandemic. We have partially addressed this by using genetic instruments (that are determined by DNA sequence and hence not variable) to derive genetically-predicted vitD levels. It is important to note that heritability of vitamin D status is high in winter (70-90%), but levels might be entirely determined by environmental factors in the summer (16). Therefore, we also included an integrative measure of ambient UVB radiation during the pandemic. However, the discriminatory power of the UVB variable is somewhat limited in this study, because UVB radiation is low at this time of the year, particularly at the high northern latitude of UK. We only used ambient UVB, and did not capture individual behavioural differences that would determine the actual level of vitamin D synthesis in the skin, such as time and time of day spent outside, clothing, choosing to walk on the sunny side of the street;. Moreover, time of year is the strongest predictor of vitD-UVB but control dates were assigned to follow the same distribution as case dates, w...

    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.

  3. Version published to 10.1101/2020.08.18.20177691v1 on medRxiv