Innate and adaptive immune responses, which are intimately related to the evolution of many infectious diseases, are influenced by the biologically active form of vitamin D. From a mechanical perspective, there are several rationales to assume that vitamin D positively modifies host responses to SARS-CoV-2, either in the early infection or subsequent hyper-inflammatory stages of COVID-19. It has been long known that vitamin D metabolites induce antiviral effects through indirect and direct mechanisms via antimicrobial peptides, immune modulation, the interaction between major viral and cellular particles, initiation of apoptosis and autophagy, and diversity of hereditary and epigenetic aspects. The remarkable overlap between the deficiency of vitamin D and risk factors for severe COVID-19, including obesity, aging, and Black or Asian ethnicity, has motivated researchers to assume that supplementation of vitamin D can be promising as a preventive or treatment agent for COVID-19. Since the outset of the pandemic, researchers have integrated literature searches and crosssectional statistical studies to appraise the vitamin D level impact of COVID-19, whereby nearly 30 observational studies have confirmed that the incidence, severity, and mortality of COVID-19 are inversely related to the serum 25OHD concentrations. Also, some recently announced clinical trials indicated that vitamin D supplementation has a positive effect on the severity of COVID-19; however, other studies, including clinical trials, have not supported that, especially if we take into account what was revealed in a recent clinical trial, i.e., airway diseases are related to the irregular metabolism of vitamin D increasing the potential of developing vitamin D deficiency due to pulmonary inflammation. Therefore, more dedicated studies are required without critical limitations to ascertain the actual effect of vitamin D in preventing and treating COVID-19, and if its effectiveness is proven, the effective dose must be determined.
Keywords: ACE2, ARDS, Antiviral, Betacoronavirus, Calcidiol, Calcitriol, Coronavirus-2, COVID-19, Epidemiological, Ethnicity, Inflammation, Innate, Mortality, Pandemic, RAS, RCTs, SARS-CoV-2, Severity, Vitamin D.