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Is vitamin D status, reflecting vitamin D levels and treatment, associated with test results for coronavirus disease 2019 (COVID-19)?
In this cohort study of 489 patients who had a vitamin D level measured in the year before COVID-19 testing, the relative risk of testing positive for COVID-19 was 1.77 times greater for patients with likely deficient vitamin D status compared with patients with likely sufficient vitamin D status, a difference that was statistically significant.
These findings appear to support a role of vitamin D status in COVID-19 risk; randomized clinical trials are needed to determine whether broad population interventions and interventions among groups at increased risk of vitamin D deficiency and COVID-19 could reduce COVID-19 incidence.
Vitamin D treatment has been found to decrease the incidence of viral respiratory tract infection, especially in patients with vitamin D deficiency. Whether vitamin D is associated with coronavirus disease 2019 (COVID-19) incidence is unknown.
To examine whether the last vitamin D status before COVID-19 testing is associated with COVID-19 test results.
Design, Setting, and Participants
This retrospective cohort study at an urban academic medical center included patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020.
Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing. Treatment changes were defined by changes in vitamin D type and dose between the date of the last vitamin D level measurement and the date of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize the most recent vitamin D status before COVID-19 testing as likely deficient (last level deficient and treatment not increased), likely sufficient (last level not deficient and treatment not decreased), and 2 groups with uncertain deficiency (last level deficient and treatment increased, and last level not deficient and treatment decreased).
Main Outcomes and Measures
The outcome was a positive COVID-19 polymerase chain reaction test result. Multivariable analysis tested whether vitamin D status before COVID-19 testing was associated with testing positive for COVID-19, controlling for demographic and comorbidity indicators.
A total of 489 patients (mean [SD] age, 49.2 [18.4] years; 366 [75%] women; and 331 [68%] race other than White) had a vitamin D level measured in the year before COVID-19 testing. Vitamin D status before COVID-19 testing was categorized as likely deficient for 124 participants (25%), likely sufficient for 287 (59%), and uncertain for 78 (16%). Overall, 71 participants (15%) tested positive for COVID-19. In multivariate analysis, testing positive for COVID-19 was associated with increasing age up to age 50 years (relative risk, 1.06; 95% CI, 1.01-1.09; P = .02); non-White race (relative risk, 2.54; 95% CI, 1.26-5.12; P = .009), and likely deficient vitamin D status (relative risk, 1.77; 95% CI, 1.12-2.81; P = .02) compared with likely sufficient vitamin D status. Predicted COVID-19 rates in the deficient group were 21.6% (95% CI, 14.0%-29.2%) vs 12.2%(95% CI, 8.9%-15.4%) in the sufficient group.
Conclusions and Relevance
In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk.
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Accepted for Publication: July 23, 2020.
Published: September 3, 2020. doi:10.1001/jamanetworkopen.2020.19722
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Meltzer DO et al. JAMA Network Open.
Corresponding Author: David O. Meltzer MD, PhD, Department of Medicine, The University of Chicago, 5841 S Maryland Ave, MC 5000, Chicago, IL 60637 (email@example.com).
Author Contributions: Drs Best and Zhang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Meltzer, Best.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Meltzer, Arora.
Critical revision of the manuscript for important intellectual content: Meltzer, Best, Zhang, Vokes, Solway.
Statistical analysis: Meltzer, Best, Zhang.
Obtained funding: Meltzer.
Administrative, technical, or material support: Meltzer, Arora.
Supervision: Meltzer, Vokes.
Conflict of Interest Disclosures: Dr Meltzer reported grants from the National Institutes of Health during the conduct of the study. Dr. Solway reports that he is studying novel compounds (unrelated to Vitamin D) for the prevention or treatment of viral infections, for which patent protection might eventually be sought. No other disclosures were reported.
Funding/Support: This study was supported by the Learning Health Care System Core of the University of Chicago/Rush University Institute for Translational Medicine (ITM) Clinical and Translational Science Award (ITM 2.0: Advancing Translational Science in Metropolitan Chicago, UL1TR002389, Solway, Contact PI) and the African American Cardiovascular Pharmacogenetic Consortium (U54-MD010723, Meltzer).
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Stephen Weber, MD (Chief Medical Officer, University of Chicago Medicine), assisted with the University of Chicago Medicine operational analyses that informed design of this study. Tim Filarski (BA) and Steven Hooper (Medical Laboratory Scientist) (University of Chicago Medicine), helped with laboratory data acquisition. No compensation was received outside of usual salary.
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