The link between vitamin D deficiency and Covid-19 in a large population

  1. Ariel Israel
  2. Assi Cicurel
  3. Ilan Feldhamer
  4. Yosef Dror
  5. Shmuel M Giveon
  6. David Gillis
  7. David Strich
  8. Gil Lavie

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Abstract

BACKGROUND

Recent studies suggest a link between vitamin D deficiency and Covid-19 infection. In our population we observe major differences in Covid-19 incidence in ethnic groups and genders in each group.

METHODS

We carried out a population-based study among 4.6 million members of Clalit Health Services (CHS). We collected results from vitamin D tests performed between 2010 and 2019 and used weighted linear regression to assess the relationship between prevalence of vitamin D deficiency and Covid-19 incidence in 200 localities. Additionally, we matched 52,405 infected patients with 524,050 control individuals of the same sex, age, geographical region and used conditional logistic regression to assess the relationship between baseline vitamin D levels, acquisition of vitamin D supplements in the last 4 months, and positive Covid-19.

RESULTS

We observe a highly significant correlation between prevalence of vitamin D deficiency and Covid-19 incidence, and between female-to-male ratio for severe vitamin D deficiency and female-tomale ratio for Covid-19 incidence in localities (P<0.001). In the matched cohort, we found a significant association between low vitamin D levels and the risk of Covid-19, with the highest risk observed for severe vitamin D deficiency. A significant protective effect was observed for members who acquired liquid vitamin D formulations (drops) in the last 4 months.

CONCLUSION

In this large observational population study, we show a strong association between vitamin D deficiency and Covid-19 occurrence. After adjustment for baseline characteristics and prior vitamin D levels, acquisition of liquid vitamin D formulations is associated with decreased risk for Covid-19 infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.04.20188268: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study has been approved by the CHS Institutional Review Board (IRB) with a waiver of informed consent, approval number: COM-0046-20.
    Consent: This study has been approved by the CHS Institutional Review Board (IRB) with a waiver of informed consent, approval number: COM-0046-20.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFemale-to-male ratio for incidence was obtained by calculating the ratio between female incidence and the male incidence in each locality.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Patients’ data were extracted and processed from CHS data-warehouse using programs developed by the first author in Python and SQL, all identifying patient data were removed prior to the statistical analyses in accordance to the protocol approved by the CHS IRB.
    Python
    suggested: (IPython, RRID:SCR_001658)

    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:
    We acknowledge our study’s limitations as being observational, noting the difficulty in eliminating all possible confounders. Notably, vitamin D supplements being available “over the counter” in pharmacies and stores, an unknown number of CHS members might have purchased vitamin D supplements with no trace in our electronic records, so our study might not have apprehended the full effects of vitamin D supplementation. Besides the link between vitamin D levels, vitamin D acquisition, and SARS-CoV-2 infection rate, our study made two intriguing observations that deserve attention. First, in our regression models, vitamin D drops were associated with decreased risk for SARS-CoV-2, but vitamin D tablet formulations were associated to increased risk. In addition, males from ultra-orthodox communities tend to have higher rates of SARS-CoV-2 infection than females, even though their measured vitamin D levels at baseline were generally not lower than in females. We propose a putative explanation for these observations: the virus port of entry is the oropharynx, it is where it first reaches mucosal membranes, initially replicates and causes its first detectable effects (anosmia, agusia, sore throat). High vitamin D concentration in the oropharynx might be the most important factor that prevents this initial infection and replication. Vitamin D in drop forms is likely mostly absorbed by the mucous membranes of the oropharynx, and the vitamin D concentration there is likely to be elevat...

    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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  2. Version published to 10.1101/2020.09.04.20188268v1 on medRxiv