COVID and Vitamin D Research Update October 2020

Currently, there is no efficacious therapy for SARS-CoV-2 infection. The understanding of the physiopathology of the infection, and risk elements for severity and mortality, is incomplete.

The use of less invasive, non-pharmacological agents, such as vitamin D, are increasingly being researched as potential aids to prevention and treatment. Early researchers into COVID-19 and vitamin D reported three striking patterns (1):

1. The innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the Renin-Angiotensin System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19's cytokine storm.

2. The groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups with darker skin living outside the tropics, those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes (2).

3. Throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates (1).

Vitamin D and the Cytokine Storm
Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signalling pathways triggered by COVID-19. In severe cases of SARS-COV-2 infection, a cytokine storm starts through cytokine overproduction and leads to Acute Respiratory Syndrome, organ failure, and potentially death. According to the evidence, Vitamin D reduces cytokine storms and the risk of Acute Respiratory Syndrome. Vitamin D also suppresses the actions of the renin-angiotensin system, which has a determining role in the inflammatory response (3). Therefore, Vitamin D intake may be beneficial for patients with SARS-COV-2 infection exposed to cytokine storm but who do not suffer from low blood pressure (4).

Research on hospital patients found that, after adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, patient mortality, C-reactive protein and an increase in lymphocytes.

Vitamin D Deficiency and Susceptibility to COVID-19
Only 9.7% of patients over 40 with sufficient levels of vitamin D succumbed to the infection compared to 20% who had low vitamin D levels. It is hypothesised that vitamin D may help modulate the immune response possibly by reducing risk for the cytokine storm in response to the virus. The researchers suggest that improving vitamin D status in the general population, and in particular hospitalized patients, has a potential benefit in reducing the risks associated with COVID-19 (5).

Vitamin D and Children
Children with COVID-19 have been found to have lower vitamin D levels than controls without the disease. Fever was significantly higher in COVID-19 patients with insufficient vitamin D compared to those with adequate vitamin D levels (6).

Dosages
A review into the effects of vitamin D on COVID-19 found that correcting vitamin D deficiency as a preventative measure is extremely safe. The researchers state the “widely recommending 2,000 IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives” (1).
COVID-19 has been compared with dengue fever, for which oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing virus replication and controlling the cytokine storm (1).
Vitamin D in Combination with Other Nutrients
In one study supplementation with a combination of vitamin D, vitamin B12 and magnesium given to older COVID-19 patients was associated with a significant reduction in the proportion of patients with deterioration requiring oxygen support, intensive care, or both (7).

Caution
There are many positives to vitamin D but there needs to be a balance between over-activation of innate immunity and the exhaustibility of the adaptive immune response. The effect of vitamin D on endothelial function and angiotensin is an on-going area of research (8).

References

1. Front Public Health. 2020 Sep 10;8:513. A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency. Benskin LL.
2. Nutr Rev. 2020 Sep 25;nuaa092. The implications of vitamin D deficiency on COVID-19 for at-risk populations. DeLuccia R et al.
3. Am J Physiol Lung Cell Mol Physiol. 2020 Sep 30. Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic. Ferder L et al.
4. Arch Physiol Biochem. 2020 Oct 8;1-9. The benefits of Vitamin D in the COVID-19 pandemic: biochemical and immunological mechanisms. Hadis Musavi et al.
5. PLoS One. 2020 Sep 25;15(9):e0239799. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. Maghbooli Z et al.
6. Pediatr Pulmonol. 2020 Oct 5. Is vitamin D deficiency a risk factor for COVID-19 in children? Kamil Yilmaz, Velat Sen.
7. 2020 Sep 8;79-80:111017. Cohort study to evaluate effect of vitamin D, magnesium, and vitamin B 12in combination on severe outcome progression in older patients with coronavirus (COVID-19). Chuen Wen Tan et al.
8. Curr Opin Clin Nutr Metab Care. 2020 Sep 29. A brief discussion of the benefit and mechanism of vitamin D supplementation on coronavirus disease 2019. Cereda E et al.