Abstract
The risks of COVID-19, whether of becoming infected, needing intensive care or dying, consistently relate inversely to vitamin D status [serum 25(OH)D concentration], but low 25(OH)D is not just due to COVID-19 since they are seen in relation to pre-pandemic 25(OH)D values, both in individual cohorts and across many populations. Furthermore, many recognised risk factors for increased COVID-19 severity themselves reduce vitamin D status [e.g., obesity, dark skin, indoor lifestyles, low socio-economic status and increasing age], which complicates data analyses. Vitamin D has many mechanistic effects likely to provide adjunctive benefits protecting against COVID-19 severity. For example, vitamin D reduces the risks of microbial infection by promoting innate immunity and reduces tissue damage in severe infections by modulating the severity of adaptive immune responses. The protective mechanistic effects of correcting vitamin D inadequacy discussed support the view that increasing vitamin D status should reduce COVID-19 risks. However, many trials of cholecalciferol treatment have failed to do so, probably because it takes many weeks to raise serum 25(OH)D levels adequately whilst the increasing clinical use of the 25(OH)D metabolite [calcifediol] in COVID-19 treatment, which raises serum 25(OH)D concentrations rapidly, has led to reports of clinical benefits in COVID-19 illness.