Evidences for a protective role of vitamin D in COVID-19

Correspondence to Professor Maurizio Cutolo; mcutolo@unige.it Introduction Vitamin D and COVID-19 A growing number of concordant reports support a protective role for vitamin D in reducing at least the risk/severity of respiratory tract infections (RTIs), especially in the influenza and COVID-19 context.1–5 Major clinical reports show that vitamin D deficiency contribute to acute respiratory distress syndrome (ARDS) SARS-CoV-2 and that case-fatality rates increase with age and the highest SARS-CoV-2 serum concentrations.6 7 In addition, the outbreak of COVID-19 seems to occur mainly in the cold winter time, when serum 25-hydroxyvitamin D (25(OH)D—calcidiol or calcifediol) concentrations are the lowest, as well as the ultraviolet B (UVB) doses, whereas the number of cases in the Southern Hemisphere near the end of summer are lower.8- Targeted 25(OH)D serum concentration measurements and vitamin D supplementation is strongly suggested have important patient and public health benefits.9 The positive role of vitamin D replacement therapy (vDRT) in reducing risk and severity in COVID-19 patients is supported by several clinical evidences and RCTs are undergoing, however, previous experiences of RCT related to vDRT are available from other lung viral infection studies and even in mechanically ventilated adult intensive care unit (ICU) patients.10–14 These important observations are corroborated by several biological/molecular mechanisms through vitamin D can generally reduce risk of infections and downregulate the immune/inflammatory reaction. The discovered presence of the VDR in activated T cells and monocytes, first suggested in 1983 that vitamin D may have a role in the function of the immune system.19 As matter of fact, vitamin D has received increased worldwide attention for its involvement in reducing risk for several chronic diseases, besides infectious diseases, including type 1 diabetes and notably autoimmune rheumatic diseases for the reason that may interfere with the immune system.20 The biological/molecular evidence for the interactions of vitamin D with the immune response is that its final active metabolite, namely calcitriol (1,25(OH)2D3), due to its structural origin from cholesterol, is molecularly considered a steroid hormone (D-hormone) like others (ie, sex hormones, cortisol) and analogously to glucocorticoids (and sex hormones) can exerts immunomodulatory/antinflammatory activities through functional cell steroid receptors21–23 (figure 1).