Serum Vitamin D levels are associated with increased COVID-19 severity markers and mortality independent of visceral adiposity

Vanegas-Cedillo, P. E.; Bello-Chavolla, O. Y.; Ramirez-Pedraza, N.; Rodriguez-Encinas, B.; Perez-Carrion, C. I.; Jasso-Avila, M. I.; Hernandez-Juarez, D.; Vargas-Vazquez, A.; Antonio-Villa, N. E.; Chapa-Ibarguengoitia, M.; Ponce de Leon, A.; Sifuentes-Osornio, J.; Aguilar-Salinas, C. A.; Mehta, R.

INTRODUCTION: Coronavirus disease (COVID-19) is a global pandemic. Vitamin D (25-OHD) deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and 25-OHD levels in patients attending a COVID-19 reference center in Mexico City are examined. METHODS: Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation (including outcomes), laboratory measurements (including 25-OHD) and a thoracic computerized tomography (including the measurement of epicardial fat thickness). Low vitamin D was defined as levels <20ng/mL (<50nmol/L) and severely low (or deficient) 25-OHD as a level [≤]12ng/mL (<30nmol/L) RESULTS: Of the 551 patients included, low 25-OHD levels were present in 45.6% and severely low levels in 10.9%. Severely low 25-OHD levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19 (OR 0.97, 95%CI 0.94-0.99, p=0.042), adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by 25-OHD levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat. CONCLUSION: Vitamin D deficiency ([≤]12ng/mL or <30nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low 25-OHD may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.