Bouillon, RogerManuel Quesada-Gomez, Jose2025-01-072025-01-072021-11-17https://hdl.handle.net/10668/25486Preclinical 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. (c) 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/VITAMIN DCALCIFEDIOLCOVID-19MORTALITYACUTE RESPIRATORY DISTRESS SYNDROMEINTENSIVE CARE TREATMENTRenin-angiotensin systemAcute lung injuryD-receptor1,25-dihydroxyvitamin d-3Tissue factorD supplementationImmune regulationD deficiencyExpressionCellsresearch article34950831open access10.1002/jbm4.105762473-4039https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jbm4.10576719677700001