Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence

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Abstract

Importance

Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment.

Objective

To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19.

Design

Retrospective cohort study

Setting

University of Chicago Medicine

Participants

Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient (last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased).

Main Outcomes and Measures

The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed.

Results

Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age≥50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%]) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19.

Conclusions and Relevance

Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.

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  1. SciScore for 10.1101/2020.05.08.20095893: (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

    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:
    Important limitations must be noted. First, the associations observed may not reflect causal effects of vitamin D deficiency on COVID-19, especially since vitamin D deficiency can reflect a range of chronic health conditions or behavioral factors that plausibly reduce the likelihood of treatment of vitamin D deficiency and increase COVID-19 risk. Nevertheless, the results are robust to including a broad set of demographic and comorbidity indicators. Our analysis also included patients treated with vitamin D2 or calcitriol, and included calcitriol levels in our definition of vitamin D deficiency, which are often used in patients with chronic kidney disease or hypoparathyroidism. In sensitivity analysis, our results generally strengthened when we omitted these patients. We also note our sample is enriched in persons with vitamin D deficiency because of the large number of African Americans, adults with chronic illness and health care workers, all living in a northern city and exposed to COVID-19 during winter. Vitamin D deficiency may be a smaller risk factor in other populations. The relative simplicity of the analysis performed here would facilitate replication of this analysis in other settings. Since vitamin D deficiency is so prevalent in the US population, and especially in persons with darker skin, who are older and nursing home residents, who are at increased risk for COVID, it seems likely that these findings might be replicated in other settings. The data presented he...

    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.