Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?

  1. Hermann Brenner
  2. Bernd Holleczek
  3. Ben Schöttker

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Abstract

The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D3 supplementation might help to reduce respiratory disease mortality. We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30–50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50–75 years from Saarland, Germany. Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3–3.2) and 3.0 (1.8–5.2) overall, 4.3 (1.3–14.4) and 8.5 (2.4–30.1) among women, and 1.9 (1.1–3.2) and 2.3 (1.1–4.4) among men. Overall, 41% (95% confidence interval: 20–58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.

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  1. Version published to 10.3390/nu12082488
  2. ScreenIT

    SciScore for 10.1101/2020.06.22.20137299: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The ESTHER study was approved by the ethics committees of the University of Heidelberg and the state medical board of Saarland, Germany.
    Consent: Written informed consent was issued by all participants.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableBriefly, 9,940 men and women, aged 50-75 years at baseline, were recruited by their general practitioners during a routine health check-up between 2000 and 2002.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study design: This investigation is based on the ESTHER study, an ongoing statewide cohort study from Saarland, Germany, details of which have been reported elsewhere (4-9).
    ESTHER
    suggested: (ESTHER, RRID:SCR_002621)
    All statistical analyses were conducted with the software package SAS, version 9.4 (Cary, North Carolina, USA).
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)

    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:
    Although we made the best attempts to adjust potential confounding factors in our analyses, the major limitation of our study is that we cannot exclude the possibility of residual confounding by imperfect measurement of confounding variables, such as smoking or physical activity, or omission of unknown confounders in this observational study. As addressed in detail elsewhere (6), interpretation of the evidence is further complicated by the fact that vitamin D deficiency could be considered both a consequence of poor health as well as a risk factor for increased vulnerability to acute disease and poor outcomes of chronic diseases among people with poor health. It is therefore paramount to critically evaluate our findings in the light of additional criteria and evidence, such as biological mechanisms and plausibility, and, in particular, in the light of data from RCTs providing vitamin D3 supplementation. Deaths from respiratory disease are mostly deaths from exacerbations of COPD which are caused by acute infections in the majority of cases or from acute respiratory infections causing pneumonia. Vitamin D3 is thought to protect from occurrence and poor outcomes of respiratory infections by several mechanisms, including enhanced physical barriers (maintenance of junction integrity), cellular innate immunity, and adaptive immunity (1). Innate and adaptive immunity are being influenced by sex hormones (12), which may explain the observed interaction of sex and 25(OH)D levels with...

    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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  3. Version published to 10.1101/2020.06.22.20137299v1 on medRxiv