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by Rod Tucker BPharm PhD
Published on 22 April 2020

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Is vitamin D status an important biomarker for symptom severity in COVID-19?

In the absence of a specific vaccine, there has been much interest in alternative treatments and strategies to help minimise the effects of infection with COVID-19.

One strategy attracting much interest in the media is the importance of achieving sufficient vitamin D levels and the topic has also been the subject of recent academic articles.1,2 While both articles discuss the potential role of vitamin D in the immune system, they also highlight the lack of direct clinical studies in those with COVID-19. However, a recent research letter3 provides some tentative evidence of the impact of vitamin D status on the severity of COVID-19 symptoms.

Vitamin D3 is produced by the action of UVB radiation on 7-dehydrocholesterol present in the skin. This only occurs in the Northern hemisphere between April and September as the sun is too low during the winter months. Vitamin D3 is subsequently converted to 25-hydroxyvitamin D (25(OH)D) and finally in the kidneys to 1,25(OH)2D (calcitriol). Although calcitriol is the active metabolite, it is the level of 25(OH)D which is measured and used to monitor vitamin D status. The possible beneficial effects of vitamin D on COVID-19 are likely mediated through its multiple actions on the immune system.1 For instance, vitamin D enhances the production of various peptides by the innate immune system, which possess anti-microbial, anti-fungal and anti-viral activity. In addition, and in response to microbial or viral infections, the innate immune system generates several pro-inflammatory cytokines including tumour necrosis factor alpha and interferon γ. Vitamin D has been shown to not only reduce the production of these pro-inflammatory cytokines but to increase the expression of anti-inflammatory cytokines by macrophages. This may be of value given the proinflammatory cytokine milieu observed in those infected with COVID-194 and how this ‘cytokine storm’ leads to acute respiratory distress syndrome.5

In light of the possible immune-enhancing effects, a recent retrospective analysis was undertaken of vitamin D status in patients with confirmed COVID-19 infection.3 Using a database from three hospitals in Southern Asian countries, the author categorised 212 cases of COVID-19 infections as mild, ordinary, severe and critical and matched these to 25(OH)D status. Normal was defined as 25(OH)D > 30ng/ml, insufficient, 21 – 29 ng/ml and deficient as <20 ng/ml. The analysis revealed that for those with mild infection, mean 25(OH)D levels were 31.2 ng/ml, ordinary, 27.4 ng/ml, severe, 21.2 ng/ml and critical the lowest at 17.1ng/ml. These differences were found to be statistically significant and hint at the possibly that patients with higher levels of 25(OH)D have less severe symptoms. Though an interesting observation, is any there other data to support the relationship between vitamin D levels and viral respiratory infections? Prior to COVID-19, several meta-analyses have explored the potential role of vitamin D in acute respiratory infections and the World Health Organisation (WHO) offered a summary of these in 2017.6 They noted how results were inconsistent with significant heterogeneity in terms of the patients included, vitamin D regimes and baseline levels, making the generalisability of the findings more difficult. WHO suggested that future trials should explore whether the benefits are achieved once vitamin D status is satisfactory.

One group who are likely to benefit from supplementing with vitamin D are those with darker or black skin who probably obtain insufficient sun exposure. Recently, a trial in 260 black American women, compared the effect of maintained and adequate 25(OH)D levels (> 30ng/ml) from supplementation vs placebo on the incidence of acute respiratory infections (ARI) over a 3-year period and found no difference between the groups.7 These results were consistent with an earlier study conducted by the same group in which patients were given either 50mcg/day of vitamin D or placebo for 12 weeks during the winter months. Although at baseline, both groups had vitamin D levels within the normal range, supplementation had no effect on the incidence of upper respiratory tract infections.8

In summary, while vitamin D is known to have immune-enhancing properties, in the absence of clinical studies, the value of either supplementing or maintaining adequate vitamin D levels to reduce the symptom burden in those with COVID-19 infection remain unclear. Nevertheless, based on the latest analysis,3 it would seem eminently sensible for clinicians to ensure that those infected with COVID-19 have adequate vitamin D levels because this may lessen the effects of the virus and possibly save more lives.

References

  1. Grant WB et al. Evidence that Vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020 Apr 2;12(4):E988.
  2. McCartney DM, Byrne DG. Optimisation of Vitamin D status for enhanced immune-protection against Covid-19. Ir Med J 2020;113(4):58.
  3. Alipio M. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (COVID-19) (April 8, 2020). https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3571484 (accessed April 2020).
  4. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506.
  5. Xu Z et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Resp Med 2020;8(4):420–22.
  6. World Health Organisation. Vitamin D for prevention of respiratory tract infections. www.who.int/elena/titles/commentary/vitamind_pneumonia_children/en/ (accessed April 2020).
  7. Aloia JF, Islam S, Mikhail M. Vitamin D and acute respiratory infections – the PODA trial. Open Forum infect Dis 2019;6(9): 1 – 6.
  8. Li-Ng M et al. A randomised controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Epidemiol Infect 2009; 137:1396–1404.


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