Vitamin D in the COVID 19 prevention and treatment: emerging evidence

The significantly higher incidence of COVID-19 on mortality and morbidity observed in the northern Italian regions as compared to the southern ones, could be partly explained by geographic variations of the prevalence of vitamin D deficiency. The present opinion paper discusses this hypothesis. The immunomodulatory effects of vitamin D have been widely established and its benefits on viral and bacterial replication have been attributed to its ability to modulate gene expression by activating the vitamin D receptor in many target cells, including immune cells, and by promoting the expression of antimicrobial peptides such as cathelicidins and beta-defensins, which are also endowed with antiviral and immunomodulatory properties. Recently, following the onset of the COVID-19 pandemic situation, many studies have shown a high prevalence of very low levels of vitamin D in patients with severe manifestations of the disease, and that high dose vitamin D administration appeared able to favourably modify the evolution of the infection. Although these studies, mainly based on cross- sectional analyses and small-scale randomized clinical studies, could not provide a definitive proof of a cause-effect relationship, it is possible to suggest that hypovitaminosis D might be considered “guilty by association” as one of the factors able to worsen the pandemic spread and its clinical impact.