Abstract
Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.
The impact of vitamin D on COVID-19 infection, hospitalization, and mortality rate has been much discussed recently, not only in the scientific community but also in the mainstream media. A large body of data, including known COVID-19 immunity pathways, vitamin D physiology and its effects on the immune system, and population-based studies linking vitamin D levels to respiratory infections, suggests that vitamin D deficiency is likely to be a significant factor in COVID-19 transmission and complications [1].
Observational data comparing outcomes from various countries report inverse association links between vitamin D levels and the severity of COVID-19 disease and resultant mortality, pointing to a possible effect of vitamin D on the immune response to infection [2]. Specifically, Spain and Italy have high rates of vitamin D deficiency and also some of the highest COVID-19 infection and mortality rates worldwide. Conversely, the Nordic countries have higher vitamin D levels as a result of formal food fortification and also lower rates of COVID-19 infection and mortality.
However, other data question such a link. For example, Greece, a country with a prevalence of vitamin D deficiency (25(OH)D < 20 ng/ml) of at least 50% over a wide age range [3], is among the countries with the lowest numbers of confirmed COVID-19 cases and deaths, while Brazil, a country on the equator, has high rates of both cases and mortality from COVID-19.
Clearly, observational data have many confounding factors and, until now, there have been no randomized controlled studies (RCTs) to test whether there is a specific role of vitamin D in COVID-19 susceptibility and complications.
The global community should await the results of well-powered randomized controlled trials showing the effect of vitamin D on COVID-19 clinical outcomes. Meanwhile, although there is currently not sufficient evidence to support recommending vitamin D to reduce the risk of COVID-19, given that many people are spending more time indoors and may not get the vitamin D they need for bone and muscle health, we consider that vitamin D–deficient patients, and, in fact, the population in general, should be advised to take a daily supplement containing 800–1000 UI: it can confer a benefit and certainly not do any harm.
References
Martineau AR, Jolliffe DA, Hooper RL et al (2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 356:i6583
Daneshkhah A, Agrawal V, Eshein A et al (2020) The possible role of vitamin D in suppressing cytokine storm and associated mortality in COVID-19 patients, medRxiv preprint. https://doi.org/10.1101/2020.04.08.20058578
Grigoriou EV, Trovas G, Papaioannou N (2018) Serum 25-hydroxyvitamin D status, quantitative ultrasound parameters, and their determinants in Greek population. Arch Osteoporos 13(1):111
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Trovas, G., Tournis, S. Vitamin D and COVID-19. Hormones 20, 207–208 (2021). https://doi.org/10.1007/s42000-020-00231-9
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DOI: https://doi.org/10.1007/s42000-020-00231-9