What was known before the pandemic is the slow process of activation of vitamin D in the liver. When vitamin D is produced in the skin as the pre-hormone cholecalciferol, or when taken by mouth or by injection, it is taken in the blood to the liver. It is there hydroxylated, that is a hydroxyl group (-OH) is added to the molecule, which then becomes 25(OH)D, also known as calcifediol (or calcidiol). It then circulates in the blood as this reservoir form. When necessary, it is taken up by appropriate cells (such as the cells of the immune system, especially T-lymphocytes) to be converted immediately into the active form 1,25(OH)D, also known as calcitriol.

We know that vitamin D from the skin or from supplements achieves higher blood levels of calcifediol, 25(OH)D, very slowly, over several days, whereas calcifediol given by mouth achieves a good blood level within 3 hours, obviously preferable to 3 or more days when critically ill.