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.
