Vitamin D Reduces Risks of Viral Infection by Enhancing The Immune Response and Maintaining Integrity of Epithelial Barriers

Vitamin D is a fat-soluble steroid hormone(22). Vitamin D modulates both the innate and adaptive immune response(23-26). In the context of disease prevention, vitamin D enhances macrophage activation, phagocytic response and production of antimicrobial peptides to stimulate the innate immune response(17, 27). It is known that vitamin D can suppress the infectiveness of a variety of enveloped virus such as the Ebola, Epstein-Barr and Hepatitis C viruses(28).Vitamin D’s anti-viral mechanism is mainly attributable to its effects in the upregulation of anti-microbial peptides such as cathelicidins (LL37) and human beta defensins 2(28). Cathelicidins and defensins act by perturbing the cell envelope of the virus, binding lipopolysaccharide residues of commensal bacteria, and inhibiting viral adhesion and entry(29-33). Lymphocytes, macrophages and dendritic cells all express the necessary enzymes that can metabolise vitamin D to its biological active form(34, 35). They are also important target cells for vitamin D as VDR is highly expressed in these cell types(35, 36). By regulating both T and B cells maturation and proliferation, it plays a pivotal role in mounting an immune response against viruses(34). Vitamin D also protects the integrity of epithelial cells lining the respiratory tract and stimulates epithelial repair, thereby alleviating lung injury associated with pneumonia that commonly complicates COVID-19 infection(37-39).
Vitamin D deficiency is common among acquired immune deficiency syndrome (AIDS) patients(40). Research study on a group of AIDS patients showed an increased mortality rate in patients who are vitamin D deficient(41, 42). The HIV virus mainly targets cluster of differentiation 4 (CD4) found on the surface of immune cells such as T helper cells, monocytes, macrophages and dendritic cells(43). The HIV virus damages and destroys these infected cells, causing a gradual depletion in CD4 positive cells, leading to immunological failure(43). There are studies which showed that vitamin D has a positive impact on improving the CD4 count in HIV patients(44). A longitudinal study in 2018 concluded that a high serum level of 25(OH)D is associated with increased CD4 count and reduces infection severity in HIV patients(45). This suggests that vitamin D supplements can enhance the recovery of human immune system. Even in AIDS patients, vitamin D supplementation has been shown to increase the level of circulating vitamin D and therefore lower the risks of bone disease and inflammation(40, 46). The use of vitamin D supplementation in HIV patients have been reported to increase the immune response against pathogens, improve immunologic recovery during combination antiretroviral therapy and reduce levels of inflammation(47, 48). Furthermore, vitamin D supplementation has been shown to reduce HIV and Hepatitis C susceptibility by inhibiting viral entry into human cells(49-52). With regards to COVID-19, vitamin D supplementation has been shown to reduce human dipeptidyl peptidase-4 receptor (DPP-4/CD26) expression(53). As DDP-4/CD26 is a receptor that interacts with the S1 domain of the COVID-19 spike glycoprotein for cell entry, vitamin D supplementation could potentially reduce the virulence of COVID-19 in humans(54, 55).