It is noteworthy that, although a recent clinical trial showed that a single high dose of vitamin D3 did not alter the length of hospital stay among patients with COVID-19 [42], the hepatic expression of CYP2R1 and CYP27A1, enzymes that convert vitamin D3 to 25-hydroxyvitamin D3 may be downregulated during critical illness, and therefore administration of vitamin D3 might fail to increase the level of 25-hydroxyvitamin D3 or 1α,25-dihydroxyvitamin D3 [43]. This evidence concerns the gene CYP27A1 and COVID-19.