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

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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.

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

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

Abstract

Until treatment and vaccine for coronavirus disease-twenty-nineteen 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 twenty-five-hydroxyvitamin D levels are associated with severe acute respiratory disease coronavirus two positivity rates. Over one hundred ninety thousand patients from all fifty states with SARS-CoV-2 results performed mid-March through mid-June, twenty twenty and matching twenty-five(OH)D results from the preceding twelve 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 one hundred ninety-one thousand seven hundred seventy-nine patients were included (median age, fifty-four years [interquartile range forty point four to sixty-four point seven]; sixty-eight percent female). The SARS-COV-2 positivity rate was nine point three percent and the mean seasonally adjusted twenty-five(OH)D was thirty-one point seven. The SARS-COV-2 positivity rate was higher in the thirty-nine thousand one hundred ninety patients with "deficient" twenty-five(OH)D values (less than twenty nanograms per milliliter) (twelve point five percent) than in the twenty-seven thousand eight hundred seventy patients with "adequate" values (thirty to thirty-four nanograms per milliliter) (eight point one percent) and the twelve thousand three hundred twenty-one patients with values greater than fifty-five nanograms per milliliter (five point nine percent). The association between twenty-five(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 and in analyses stratified by all studied demographic factors. The association between lower SARS-COV-2 positivity rates and higher circulating twenty-five(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio zero point nine eight four per nanogram per milliliter increment; p less than zero point zero zero one). SARS-COV-2 positivity is strongly and inversely associated with circulating twenty-five(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.

Introduction

Introduction

Studies suggest an association between vitamin D deficiency and risk of viral upper respiratory tract infections and mortality from coronavirus disease-twenty-nineteen. This relationship is anticipated, given that vitamin D has numerous actions affecting the innate and adaptive immune systems. Respiratory monocytes/macrophages and epithelial cells constitutively express the vitamin D receptor. Acting through this receptor, vitamin D may be important in protection against respiratory infections. In addition, an important action of vitamin D is suppressing excessive cytokine release that can present as a "cytokine storm," a common cause of COVID-19-related morbidity and mortality. The role of vitamin D supplementation in reducing the risk of infection by severe acute respiratory disease coronavirus two has not been studied. Better understanding of the relation between vitamin D status and SARS-CoV-2 NAAT positivity rates is appropriate before evaluating this potential intervention.

Previous studies examined latitude-related differences in COVID-19 outcomes related to vitamin D. However, to our knowledge, only two studies investigated the direct relationship between vitamin D status and SARS-CoV-2 positivity, and these came to opposite conclusions. Both were based on small numbers of paired SARS-CoV-2 and twenty-five(OH)D results, and neither involved US patients. In this study, we evaluated the association of circulating twenty-five-hydroxyvitamin D levels, a measure of vitamin D status, with positivity for SARS-CoV-2 as assessed with nucleic acid amplification testing.

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