Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint

Abstract

The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.

The Power of Vitamin D: Is the Future in Precision Nutrition through Personalized Supplementation Plans?

“…Several other nutrients are necessary for vitamin D to function properly in our body. These include calcium (vitamin D helps the absorption and use of calcium in the body, a crucial nutrient for building and maintaining healthy bones and teeth) [ 178 ], magnesium (required for vitamin D activation, and it helps to regulate calcium levels in the body) [ 179 ], phosphorus (another mineral critical for bone health, and it works together with calcium and vitamin D to keep bones strong) [ 180 ], vitamin K 2 (helps to regulate calcium metabolism in the body, and it works together with vitamin D to support bone health) [ 181 ], zinc (mineral that participates in the functioning of the immune system, and it is needed for the proper metabolism of vitamin D) [ 182 ], and vitamin A (participates in controlling gene expression and cell differentiation, and it works together with vitamin D to support bone health) [ 183 ]. Therefore, a balanced diet that includes a variety of nutrient-rich foods must be upheld to maintain optimal health.…”

Zinc, Magnesium and Vitamin K Supplementation in Vitamin D Deficiency: Pathophysiological Background and Implications for Clinical Practice

“…A lot of evidence has showed the antiviral, immunomodulatory and anti-inflammatory activity of Zn [ 39 ]. It impacts the survival, proliferation, and maturation of various cells involved in both adaptive and innate immunity; regulates chronic inflammation by decreasing inflammatory cytokines and antibody production; mitigates oxidative stress by upregulating antioxidant enzymes synthesis; helps to maintain natural tissue barriers like the respiratory epithelium (preventing the entry of pathogens); enhances mucociliary clearance of viruses like the coronaviruses, removing the viral particle and reducing the risk of secondary infections; potentially exhibits antiviral activity by directly preventing viral replication; and is also involved in neurotransmission, affecting learning and memory processes [ 24 , 25 , 36 , 37 , 39 , 43 , 44 , 45 , 46 ]. Interestingly, Zn has an ambivalent role: in the free form (as a transition metal), it can generate reactive oxygen species.…”

“…It appears that Zn homeostasis and VitD functioning are linked. Zn can regulate the expression of vitamin D-dependent genes via contributing to VDR conformational changes and intensifying the activity of specific vitamin D-dependent promoters; therefore, Zn is considered an essential cofactor for VitD activity [ 35 , 44 ]. On the other hand, VitD can directly augment the expression of Zn transporters, such as ZnT10; an upregulation of the ZnT10 protein allows Zn to migrate out of the cytosol, and increased concentrations can be available for extracellular use [ 35 , 44 ].…”

“…Zn can regulate the expression of vitamin D-dependent genes via contributing to VDR conformational changes and intensifying the activity of specific vitamin D-dependent promoters; therefore, Zn is considered an essential cofactor for VitD activity [ 35 , 44 ]. On the other hand, VitD can directly augment the expression of Zn transporters, such as ZnT10; an upregulation of the ZnT10 protein allows Zn to migrate out of the cytosol, and increased concentrations can be available for extracellular use [ 35 , 44 ]. However, it was also hypothesized that, by improving the intracellular Zn concentrations, VitD can mitigate oxidative damage; and increased intracellular oxidative stress is known to contribute to the development of many pathologies, such as cardiovascular disease, neurological disorders, cancer, diabetes mellitus or ischemia [ 46 ].…”

Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection

“…Importantly, even if circulating vitamin D levels mainly depend on the kidney hydroxylation step, also other extra-renal tissues express the unique 1α-hydroxylase CYP27B1, the enzyme needed to assure the final activating hydroxylation, thus allowing vitamin D autocrine and paracrine hormonal actions. Among the "non-canonical" targets of vitamin D, the most studied is the immune system, where it exerts both immunomodulating and anti-inflammatory actions [92][93][94]98,101,103].…”