JAMA Netw Open. 2021;4(3):e214117. https://bit.ly/3zopFZ4
This prospective observational cohort study (n=4638) measured vitamin D level in the year before undergoing COVID-19 testing. The risk of a positive COVID-19 test in Black, but not White, individuals was 2.64-fold higher if vitamin D level was 3040 ng/ml compared to > 40 ng/ml.
Vitamin D may improve immune function and decrease inflammation. A meta-analysis of randomized clinical trials showed that daily or weekly vitamin D supplementation decreased risk of viral respiratory infections, especially in those who were deficient in vitamin D, but also in those with normal levels. Furthermore, vitamin D deficient levels have been associated with higher COVID-19 incidence and worse outcomes, especially in Black, Hispanic, and other non-White populations, who have also borne a disproportionately high burden of COVID-19. Both deficiency (< 20 ng/ml) and insufficiency (20 to <30 ng/ml) of 25-hydroxyvitamin D are more common in Black individuals than White individuals. Almost half of the worlds population has vitamin D levels <30 ng/ml.
From the very beginning of the COVID-19 epidemic, the question was raised whether vitamin D levels higher than the sufficient level (30 ng/mL) are associated with risk of COVID-19 infection. This research extends an earlier study showing that vitamin D deficiency (<20 ng/ml) is associated with higher risk of COVID-19 infection. All-cause mortality and other outcomes may be better with vitamin D levels 4060 ng/ml, at least in some racial groups. It remains unknown whether increasing vitamin D level >40 ng/ml affects COVID-19 risk. That vitamin D levels are associated with COVID-19 infection, especially in individuals taking vitamin D supplements, supports the idea that supplementation might decrease COVID-19 risk by increasing vitamin D levels. The significant association only in Black individuals might reflect their higher COVID-19 risk, to which socioeconomic factors and structural inequities clearly contribute.
However, we should be aware that, beyond its traditional functions in calcium homeostasis and bone health, Vitamin D status has been associated with multiple health outcomes, ranging from metabolic syndrome traits to reproductive ageing, fetal growth and cancer risks. A major issue of studying circulating vitamin D in observational studies is that lower levels are strongly influenced by many potential confounding factors, such as higher BMI (due to storage in adipose tissue), exercise, household crowding and skin colour (which all affect sunlight exposure). The lack of confirmation of most of these benefits in trials have so far limited the translation of this evidence to public health policies. Hence, the authors will now recruit participants for two clinical trials to test the efficacy of vitamin D supplements to prevent COVID-19 and we eagerly await those results.