Vitamin D Regulation of Immune Function.

PURPOSE OF REVIEW: To review the mechanisms by which vitamin D and its metabolites regulate the immune system to facilitate the ability of the body to prevent and/or treat SARS-CoV2 and other respiratory infections and encourage further research into the role that vitamin D supplementation plays in preventing/treating such infections. RECENT FINDINGS: Vitamin D deficiency is associated with an increased risk of SARS-CoV2 and other respiratory infections. Clinical trials in general demonstrate that correction of vitamin D deficiency reduces the risk of hospitalization, ICU admission, and death from SARS-CoV2 infection. The airway epithelium and alveolar macrophages express the enzyme, CYP27B1, that produces the active metabolite of vitamin D, 1,25(OH)2D, and the vitamin D receptor, VDR. Vitamin D and its metabolites promote the innate immune response, which provides the first line of defense against viral and bacterial infections while restricting the adaptive immune response, which if unchecked promotes the inflammatory response leading to the acute respiratory distress syndrome and death. The rationale for treating vitamin D deficiency to reduce the risk of SARS-CoV2 infection and supplementing patients with vitamin D early in the course of SARS-CoV2 infection rests primarily on the ability of vitamin D metabolites to promote an effective immune response to the infection.

Vitamin D regulation of immune function during covid-19.

Covid-19 has to date infected a confirmed 275 million people with 5.4 million, now dead, with the count rising every day. Although the virus, SARS-CoV2, causing Covid-19 infects many cells in the body, its infection of the upper and lower respiratory tract (upper airway epithelia and pulmonary alveolar pneumocytes and macrophages) causing what is now called a cytokine storm in the lungs is the major cause of morbidity and mortality. This results from a dysregulation of the innate immune system with an outpouring of proinflammatory cytokines and chemokines leading to abnormal activation of the adaptive immune pathway. Airway epithelia constitutively expresses CYP27B1, the enzyme producing the active vitamin D metabolite, 1,25(OH)2D, and the vitamin D receptor (VDR) for which 1,25(OH)2D is the ligand. Pulmonary alveolar macrophages, on the other hand, are induced to express both CYP27B1 and VDR by various pathogens including viruses and cytokines released from infected epithelia and other immune cells. Although not demonstrated for corona viruses like SARS-CoV2, for other viruses and other respiratory pathogens activation of innate immunity leading to increased local 1,25(OH)2D production has been shown to enhance viral neutralization and clearance while modulating the subsequent proinflammatory response. Whether such will be the case for SARS-CoV2 remains to be seen, but is currently being proposed and investigated. This mini review will discuss some of the mechanisms by which vitamin D may help reduce morbidity and mortality in this devastating pandemic.