Vitamin D Endocrine System and COVID‐19

Preclinical data strongly suggest that the vitamin D endocrine system (VDES) may have extraskeletal effects. Cells of the immune and cardiovascular systems and lungs can express the vitamin D receptor, and overall these cells respond in a coherent fashion when exposed to 1,25‐dihydroxyvitamin D, the main metabolite of the VDES. Supplementation of vitamin D‐deficient subjects may decrease the risk of upper respiratory infections. The VDES also has broad anti‐inflammatory and anti‐thrombotic effects, and other mechanisms argue for a potential beneficial effect of a good vitamin D status on acute respiratory distress syndrome, a major complication of this SARS‐2/COVID‐19 infection. Activation of the VDES may thus have beneficial effects on the severity of COVID‐19. Meta‐analysis of observational data show that a better vitamin D status decreased the requirement of intensive care treatment or decreased mortality. A pilot study in Cordoba indicated that admission to intensive care was drastically reduced by administration of a high dose of calcifediol early after hospital admission for COVID‐19. A large observational study in Barcelona confirmed that such therapy significantly decreased the odds ratio (OR) of mortality (OR = 0.52). This was also the conclusion of a retrospective study in five hospitals of Southern Spain. A retrospective study on all Andalusian patients hospitalized because of COVID‐19, based on real‐world data from the health care system, concluded that prescription of calcifediol (hazard ratio [HR] = 0.67) or vitamin D (HR = 0.75), 15 days before hospital admission decreased mortality within the first month. In conclusion, a good vitamin D status may have beneficial effects on the course of COVID‐19. This needs to be confirmed by large, randomized trials, but in the meantime, we recommend (rapid) correction of 25 hydroxyvitamin D (25OHD) deficiency in subjects exposed to this coronavirus. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.