SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels

Abstract

Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ≥55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.

Fig 1. SARS-CoV-2 NAAT positivity rates and circulating 25(OH)D levels in the total population.

Smooth line represents the weighted second order polynomial regression fit to the data associating circulating 25(OH)D levels (x) and SARS-CoV-2 positivity rates (y) where: y = 0.2029–0.0052*x + 4.8e-05*x²; R² = 0.96. SI conversion factor: 1 ng/mL = 0.400641 nmol/L.

Fig 2

SARS-CoV-2 NAAT Positivity Rates and Circulating 25(OH)D Levels, (A) by Latitude Region and (B) Predominately Black non-Hispanic, Hispanic, and White non-Hispanic Zip Codes. Smooth lines represent the weighted second order polynomial regression fit to the data associating circulating 25(OH)D levels (x) and SARS-CoV-2 positivity rates (y) where: Northern: y = 0.2544–0.0055*x + 5.2e-05*x²; R² = 0.94. Central: y = 0.1745–0.0049*x + 4.7e-05*x²; R² = 0.94. Southern: y = 0.1693–0.0052*x + 5.2e-05*x²; R² = 0.90. Black non-Hispanic: y = 0.2948–0.0067*x + 5.8e-05*x²; R² = 0.87. Hispanic: y = 0.2873–0.0083*x + 8.5e-05*x²; R² = 0.95. White non-Hispanic: y = 0.1219–0.0021*x + 1.5e-05*x²; R² = 0.92. SI conversion factor: 1 ng/mL = 0.400641 nmol/L.

Fig 3

SARS-CoV-2 NAAT Positivity Rates and Circulating 25(OH)D Levels by (A) Age Group and (B) Sex. Smooth lines represent the weighted second order polynomial regression fit to the data associating circulating 25(OH)D levels (x) and SARS-CoV-2 positivity rates (y) where: Age <60: y = 0.2161–0.0058*x + 5.6e-05*x²; R² = 0.94. Age ≥60: y = 0.1515–0.0030*x + 2.4e-05*x²; R² = 0.91. Female: y = 0.1837–0.0045*x + 3.9e-05*x²; R² = 0.94. Male: y = 0.2445–0.0068*x + 6.9e-05*x²; R² = 0.94. SI conversion factor: 1 ng/mL = 0.400641 nmol/L.