Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results
Authors: David O Meltzer
Tamara Vokes
Vineet Arora
Julian Solway
Hui Zhang
Thomas J Best
Journal: JAMA Network Open (2020)
Discipline: CLINICAL MEDICINE
Keywords: Vitamin D; COVID-19; respiratory tract infection; deficiency; incidence
Affiliations: Department of Medicine, University of Chicago, Chicago, Illinois., Center for Health and the Social Sciences, University of Chicago, Chicago, Illinois.

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. 

Retracted: No

PubPeer comments:
 FACT: Highly selected sample, 500 patients of a single center. Only one vitamin D test at a random season. OBJECTION: Berkson Bias, Residual confounding. REF: https: www.jstor.org stable 3002000?origin=crossref https: onlinelibrary.wiley.com doi abs 10.1002 sim.4780111308 *** FACT: Vitamin D categorization into low and high is controversial. OBJECTION: Binary exposure misclassification. REF: http: www.biomedcentral.com 1471-2288 12 21u00a9 2012 *** FACT: Threshold value of P 0.05 is arbitrary. OBJECTION: Over- underestimation of effects. REF: https: www.tandfonline.com doi full 10.1080 00031305.2018.1527253 https: www.nature.com articles s41562-017-0189-z *** FACT: Study not pre-registered. OBJECTION: Data dredging, publication bias. REF: https: www.sciencemag.org news 2018 09 more-and-more-scientists-are-preregistering-their-studies-should-you https: en.wikipedia.org wiki Data_dredging *** FACT: Most relevant paper in the field not being cited. OBJECTION: Reverse causality. The more ill will have lower values due to A. less sun exposure outdoors and B. higher pro-hormone consumption. REF: https: www.bmj.com content 348 bmj.g2035 https: europepmc.org article med 23454726 ,