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).