Vitamin D Endocrine System and COVID‐19

Abstract

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 realworld 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.

Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study

“…Treatment with calcifediol administered alone improved the evolution of COVID-19, reducing the need for ICU treatment and poor prognosis, confirming in real life throughout the pandemic the results obtained in the pilot study of calcifediol [ 14 ]. These results are similar to those obtained in observational studies when calcifediol was administered at high doses [ 15 , 16 , 27 ] and is consistent with the effects of the VDES on most tissues, including lung and immune cells [ 13 , 28 ]. However, when calcifediol has been used at strictly replacement doses, the clinical response is more limited [ 29 ].…”

“…The VDES is active in all targets of damage by COVID-19, such as the lung and gastrointestinal, epithelium vascular and immune cells. These cells express both 1α-hydroxylase and the VDR, allowing these cells to locally activate 25OHD into 1,25(OH)2D and regulate a large number of their genes [ 28 , 32 ]. If the availability of 25OHD is decreased, whatever the causal mechanism, the well-established protective functions of the VDES against COVID-19 are lost [ 28 , 32 ].…”

“…VDR activation also promotes an antioxidant effect in monocytes by up-regulating glutathione reductase and glutamate–cysteine ligase, which reduces oxygen radical production. In addition, activation of the VDR contributes to maintaining the integrity of the pulmonary epithelial barrier and stimulating its repair [ 28 , 32 , 35 ].…”

Fibroblast Growth Factor 23 in COVID-19: An Observational Study

“…Evidence documenting the role of vitamin D deficiency in the risk of infection by COVID-19 comes mainly from association studies, while in vitro or preclinical data regarding the protection provided by 1,25(OH)2D3 are extremely limited. Furthermore, despite the protective activity of 1,25(OH)2D3 in viral infections, there is evidence that its activity inhibits only certain viral infections, and the findings of its activity in in vitro infections of human cells by COVID-19 remain unreliable [ 30 - 31 ].…”

Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis

“…In the context of the association between vitamin D and infection, it is important to note that a definitive correlation between the impact of diminished or elevated levels of vitamin D and the occurrence or gravity of the infection remains elusive. On the other hand, vitamin D has been observed to attenuate the activation of the acquired immune system, to contribute to the synthesis of defensins, to be pivotal for enhancing the phagocytic activity of macrophages towards pathogens [ 9 ] and to modulate the immune system response by regulating the inflammatory cascade [ 10 ].…”