[Skip to Content]
[Skip to Content Landing]

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

Educational Objective
To understand the association between Vitamin D and COVID-19
1 Credit CME
Key Points

Question  Is vitamin D status, reflecting vitamin D levels and treatment, associated with test results for coronavirus disease 2019 (COVID-19)?

Findings  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.

Meaning  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.


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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

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 (dmeltzer@medicine.bsd.uchicago.edu).

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.

COVID-19 corona virus pandemic. Worldometer. Updated August 12, 2020. Accessed August 12, 2020. https://www.worldometers.info/coronavirus
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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.mm6915e3PubMedGoogle ScholarCrossref
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. https://www.medpagetoday.com/infectiousdisease/covid19/85596
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. https://www.cdc.gov/nchs/nvss/vsrr/COVID19/index.htm
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. https://www.cdc.gov/coronavirus/2019-ncov/hcp/long-term-care.html
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.mm6915e6PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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/NEJMoa2001316PubMedGoogle ScholarCrossref
Cumulative number of patients diagnosed with coronavirus disease (COVID-19) in Japan as of August 7, 2020. Statista. Accessed August 12, 2020. https://www.statista.com/statistics/1096478/japan-confirmed-cases-of-coronavirus-by-state-of-health
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
Hunt  K. Britons urged to take vitamin D while sheltering inside during the pandemic. Published April 23, 2020. Accessed April 27, 2020. https://www.cnn.com/2020/04/23/health/vitamin-d-uk-coronavirus-wellness/index.html
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. https://www.foxnews.com/opinion/former-cdc-chief-tom-frieden-coronavirus-risk-may-be-reduced-with-vitamin-d
Medical societies advise on vitamin D in midst of COVID-19. Medscape. Published July 10, 2020. Accessed July 10, 2020. https://www.medscape.com/viewarticle/933715
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. https://www.cdc.gov/coronavirus/2019-ncov/lab/testing.html
Viracor. Coronavirus (COVID-19) SARS-CoV-2 PCR. Accessed July 13, 2020. https://www.viracor-eurofins.com/test-menu/8300-coronavirus-covid-19-sars-cov-2-rt-pcr/
Roche Diagnostics. cobas SARS-CoV-2 test (for the COVID-19 coronavirus). Accessed July 13, 2020. https://diagnostics.roche.com/us/en/products/params/cobas-sars-cov-2-test.html
Roche Diagnostics. cobas Elecsys Vitamin D total II assay. Accessed July 15, 2020. https://diagnostics.roche.com/se/sv/products/params/elecsys-vitamin-d-total-ii.html
Mayo Clinic Laboratories. Test ID: DHVD: 1,25-dihydroxyvitamin D, serum. Accessed July 15, 2020. https://www.mayocliniclabs.com/test-catalog/Performance/8822
Del Valle  HB , Yaktine  AL , Taylor  CL , Ross  AC , eds.  Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press; 2011.
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 PubMedGoogle ScholarCrossref
Healthcare Cost and Utilization Project (HCUP). Elixhauser Comorbidity Software for ICD-10-CM (beta version).Version 2020 v1. Accessed April 8, 2020. https://www.hcup-us.ahrq.gov/toolssoftware/comorbidityicd10/comorbidity_icd10.jsp
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 PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
Pregibon  D . Data Analytic Methods for Generalized Linear Models. Dissertation. University of Toronto; 1979; 43.
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.200410165PubMedGoogle ScholarCrossref
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 PubMedGoogle ScholarCrossref
Institute of Medicine.  Dietary Reference Intakes for Calcium and Vitamin D. The National Academies Press; 2011.
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.mm6924e2PubMedGoogle ScholarCrossref
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.mm6918e1PubMedGoogle ScholarCrossref
Sassi  F , Tamone  C , D’Amelio  P .  Vitamin D: nutrient, hormone, and immunomodulator.   Nutrients. 2018;10(11):1656. doi:10.3390/nu10111656PubMedGoogle ScholarCrossref
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.
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.1001176PubMedGoogle Scholar
Yin  K , Agrawal  DK .  Vitamin D and inflammatory diseases.   J Inflamm Res. 2014;7:69-87. doi:10.2147/JIR.S63898PubMedGoogle Scholar
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/ijms20225811PubMedGoogle ScholarCrossref
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)30628-0PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.