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

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 to those with unlikely sufficient vitamin D status, a difference that was statistically significant. 

Of 4314 patients tested for COVID-19 during the study period, a total of 489 patients (mean 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. 

COVID-19 testing between March 3, 2020 and April 10, 2020.

• One hundred and seventy-two (35%) individuals had vitamin D deficiency. Compared with patients who were not vitamin D deficient, patients who were vitamin D deficient were more likely to be younger (age 45.9 years vs 51.0 years), race other than White (142 of 172 [83%] vs 189 of 317 [60%]), and to have received vitamin D2 supplementation (44 of 172 [26%] vs 32 of 317 [10%]) and less likely to have received vitamin D3 supplementation (45 of 172 [26%] vs 148 of 317 [47%]). 
• Combining vitamin D deficiency and treatment after the most recent vitamin D level to assess vitamin D status before COVID-19 testing, 124 (25%) patients were likely deficient, 287 (59%) were likely sufficient, and 48 (10%) and 30 (6%) were in the 2 groups with uncertain deficiency. 
• Overall, 71 (15%) participants tested positive for COVID-19.  
• Among the 172 (35%) participants whose most recent vitamin D level was deficient, 32 (19%) tested positive for COVID-19 compared with 39 (12%) for participants whose last vitamin D level was not deficient. 
• Patients with likely deficient vitamin D status at the time of COVID-19 testing had an increased relative risk of testing positive for COVID-19 (relative risk, 1.77; 95%CI, 1.12-2.81; P = .02) compared with patients with likely sufficient status at the time of COVID-19 testing, for an estimated mean rate in the deficient group of 21.6% (95%CI, 14.0%-29.2%) vs 12.2% (95%CI, 8.9%-15.4%) in the sufficient group 

• Causality in the association between vitamin D status and the risk of COVID-19 cannot be concluded from a retrospective study.  
• Vitamin D deficiency may be a consequence associated with a range of chronic health conditions or behavioral factors that plausibly increase COVID-19 risk. 
• Data was limited to those available in the UCM electronic health record. 
• Only a few individuals received higher doses of vitamin D3 or had relatively
• high vitamin D levels, limiting power to assess whether vitamin D dose or levels are associated with the likelihood of COVID-19. 
• The patient sample is enriched in persons with vitamin D deficiency because of the large number of African American individuals, adults with chronic illness, and health care workers, all living in a northern city and exposed to COVID-19 during winter. Vitamin D deficiency is highly prevalent in the US but could be a smaller risk factor in other populations. 

The findings of this study suggest a role of vitamin D status, based on deficiency of levels and treatment, in risk of COVID-19 infection. Randomized clinical trials of interventions to reduce vitamin D deficiency are needed to determine if those interventions could reduce COVID-19 incidence, including both broad population interventions and interventions among groups at increased risk of vitamin D deficiency and/or COVID-19.

• This is a retrospective cohort study conducted at an urban academic medical center (University of Chicago Medicine). 
• Electronic health records were used to gather demographic, comorbidity, laboratory, and medication data within 1 year before the date of their first COVID-19 test. Age, sex, race/ethnicity, and data to calculate BMI were also obtained from the electronic health record. 
• COVID-19 test status was determined by any positive COVID-19 polymerase chain reaction test result. 
• Patients were deemed to be vitamin D deficient if their most recent serum vitamin D levels within 1 year before their first COVID-19 tests were < 50 nmol/L for 25-hydroxycholecalciferol or < 43.2 pmol/L for 1,25-dihydroxycholecalciferol. 
• Vitamin D treatment was defined by report in the electronic health record of vitamin D either in the patient medication list or prescription orders. 
• Investigators combined the data on last vitamin D level measurements with changes in treatment after that last vitamin D level to assign each patient to 1 of 4 categories, reflecting their likelihood of being vitamin D deficient at the time of COVID-19 testing: 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). 
• ICD-10-CM codes for comorbidities were identified in the medical record over a 2-year period and include, hypertension, diabetes, chronic pulmonary disease, pulmonary circulation disorders, depression, immunosuppression, liver disease, and chronic kidney disease. 

Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw Open. 2020 Sep 1;3(9):e2019722. doi: 10.1001/jamanetworkopen.2020.19722. PMID: 32880651; PMCID: PMC7489852. https://pubmed.ncbi.nlm.nih.gov/32880651/