Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results

David O Meltzer, Thomas J Best, Hui Zhang, Tamara Vokes, Vineet Arora, Julian Solway, David O Meltzer, Thomas J Best, Hui Zhang, Tamara Vokes, Vineet Arora, Julian Solway

Abstract

Importance: 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.

Objective: 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.

Exposures: 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.

Results: 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.

Conflict of interest statement

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.

Figures

Figure.. Most Recent Vitamin D Levels Before…
Figure.. Most Recent Vitamin D Levels Before COVID-19 Test

References

    1. COVID-19 corona virus pandemic. Worldometer. Updated August 12, 2020. Accessed August 12, 2020.
    1. Grant WB, Lahore H, McDonnell SL, et al. . Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988. doi:10.3390/nu12040988
    1. Martineau AR, Jolliffe DA, Hooper RL, et al. . Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
    1. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54. doi:10.1016/j.nutres.2010.12.001
    1. Garg S, Kim L, Whitaker M, et al. . Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019: COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458-464. doi:10.15585/mmwr.mm6915e3
    1. Umhau JC. Casting sunlight on an epidemic: is vitamin D a critical host factor to prevent COVID-19? MedPage Today. Published March 25, 2020. Accessed April 13, 2020.
    1. NCHS, National Vital Statistics System Provisional death counts for coronavirus disease (COVID-19). Centers for Disease Control and Prevention. Updated August 12, 2020. Accessed August 12, 2020.
    1. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases Preparing for COVID-19 in nursing homes. Updated August 12, 2020. Accessed August 12, 2020.
    1. CDC COVID-19 Response Team Characteristics of health care personnel with COVID-19 - United States, February 12-April 9, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):477-481. doi:10.15585/mmwr.mm6915e6
    1. Huotari A, Herzig KH. Vitamin D and living in northern latitudes—an endemic risk area for vitamin D deficiency. Int J Circumpolar Health. 2008;67(2-3):164-178. doi:10.3402/ijch.v67i2-3.18258
    1. Elliott ME, Binkley NC, Carnes M, et al. . Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D. Pharmacotherapy. 2003;23(6):702-710. doi:10.1592/phco.23.6.702.32182
    1. Sowah D, Fan X, Dennett L, Hagtvedt R, Straube S. Vitamin D levels and deficiency with different occupations: a systematic review. BMC Public Health. 2017;17(1):519. doi:10.1186/s12889-017-4436-z
    1. Li Q, Guan X, Wu P, et al. . Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199-1207. doi:10.1056/NEJMoa2001316
    1. Cumulative number of patients diagnosed with coronavirus disease (COVID-19) in Japan as of August 7, 2020. Statista. Accessed August 12, 2020.
    1. Ginde AA, Sullivan AF, Mansbach JM, Camargo CA Jr. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010;202(5):436.e1-436.e8. doi:10.1016/j.ajog.2009.11.036
    1. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M; Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society . Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122(2):398-417. doi:10.1542/peds.2007-1894
    1. Nakamura K. Vitamin D insufficiency in Japanese populations: from the viewpoint of the prevention of osteoporosis. J Bone Miner Metab. 2006;24(1):1-6. doi:10.1007/s00774-005-0637-0
    1. Hunt K. Britons urged to take vitamin D while sheltering inside during the pandemic. Published April 23, 2020. Accessed April 27, 2020.
    1. Frieden T. Former CDC Chief Dr. Tom Frieden: coronavirus infection risk may be reduced by vitamin D. Fox News, Opinion. Published March 23, 2020. Accessed April 13, 2020.
    1. Medical societies advise on vitamin D in midst of COVID-19. Medscape. Published July 10, 2020. Accessed July 10, 2020.
    1. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. CDC diagnostic tests for COVID-19. Centers for Disease Control and Prevention. Updated August 5, 2020. Accessed August 12, 2020.
    1. Viracor. Coronavirus (COVID-19) SARS-CoV-2 PCR. Accessed July 13, 2020.
    1. Roche Diagnostics cobas SARS-CoV-2 test (for the COVID-19 coronavirus). Accessed July 13, 2020.
    1. Roche Diagnostics. cobas Elecsys Vitamin D total II assay. Accessed July 15, 2020.
    1. Mayo Clinic Laboratories. Test ID: DHVD: 1,25-dihydroxyvitamin D, serum. Accessed July 15, 2020.
    1. Del Valle HB, Yaktine AL, Taylor CL, Ross AC, eds. Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press; 2011.
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. ; Endocrine Society . Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. doi:10.1210/jc.2011-0385
    1. Healthcare Cost and Utilization Project (HCUP). Elixhauser Comorbidity Software for ICD-10-CM (beta version).Version 2020. v1. Accessed April 8, 2020.
    1. Zhang JX, Iwashyna TJ, Christakis NA. The performance of different lookback periods and sources of information for Charlson comorbidity adjustment in Medicare claims. Med Care. 1999;37(11):1128-1139. doi:10.1097/00005650-199911000-00005
    1. McNutt LA, Wu C, Xue X, Hafner JP. Estimating the relative risk in cohort studies and clinical trials of common outcomes. Am J Epidemiol. 2003;157(10):940-943. doi:10.1093/aje/kwg074
    1. Pregibon D. Data Analytic Methods for Generalized Linear Models Dissertation. University of Toronto; 1979; 43.
    1. Blizzard L, Hosmer DW. Parameter estimation and goodness-of-fit in log binomial regression. Biom J. 2006;48(1):5-22. doi:10.1002/bimj.200410165
    1. Hastie CE, Mackay DF, Ho F, et al. . Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020;14(4):561-565. doi:10.1016/j.dsx.2020.04.050
    1. Institute of Medicine Dietary Reference Intakes for Calcium and Vitamin D. The National Academies Press; 2011.
    1. Stokes EK, Zambrano LD, Anderson KN, et al. . Coronavirus disease 2019 case surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(24):759-765. doi:10.15585/mmwr.mm6924e2
    1. Gold JAW, Wong KK, Szablewski CM, et al. . Characteristics and clinical outcomes of adult patients hospitalized with COVID-19 - Georgia, March 2020. MMWR Morb Mortal Wkly Rep. 2020;69(18):545-550. doi:10.15585/mmwr.mm6918e1
    1. Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11):1656. doi:10.3390/nu10111656
    1. Greger JL. Effect of Variations in Dietary Protein, Phosphorus, Electrolytes and Vitamin D on Calcium and Zinc Metabolism: Nutrient Interactions. Marcel Dekker; 1988:205-228.
    1. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6(11):e1001176. doi:10.1371/journal.ppat.1001176
    1. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014;7:69-87. doi:10.2147/JIR.S63898
    1. Roffe-Vazquez DN, Huerta-Delgado AS, Castillo EC, et al. . Correlation of vitamin D with inflammatory cytokines, atherosclerotic parameters, and lifestyle factors in the setting of heart failure: a 12-month follow-up study. Int J Mol Sci. 2019;20(22):5811. doi:10.3390/ijms20225811
    1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK . COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0

Source: PubMed

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