MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19

Abstract

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.

Figure 1

Antimicrobial actions of vitamin D. Schematic showing possible macrophage responses to microbial infection. Pattern recognition receptors such as toll-like receptors (TLR) signal responses to pathogens. This includes transcriptional induction of 1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR). Serum 25-hydroxyvitamin D (25-OHD) bound to vitamin D binding protein (DBP) allows intracellular access of free 25-OHD for conversion to 1,25 (OH)₂D, which then bind to VDR. Transcriptional responses to 1,25 (OH)₂D (shown with red arrows) include induction of cathelicidin and β-defensin 2 (DEFB4), NOD2, and nitric oxide (NO). Intracellular iron (Fe) is exported via ferroportin which is targeted for degradation by hepcidin. The bacterial cell wall product muramyl dipeptide binds to NOD2.

Figure 2

Autophagy and antivirobial actions of vitamin D. Schematic showing possible macrophage responses to viral infection. This includes transcriptional induction of 1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR). Serum 25-hydroxyvitamin D (25-OHD) bound to vitamin D binding protein (DBP) allows intracellular access of free 25-OHD for conversion to 1,25 (OH)₂D, which then bind to VDR. Transcriptional responses to 1,25 (OH)₂D (shown with red arrows) include induction of cathelicidin and β-defensin 2 (DEFB4), nitric oxide (NO) and intracellular calcium (Ca).