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What about incorporating vitamins D and C supplementation in the prevention and treatment of COVID-19? The immune response pathway

Recently, Thevarajan et al. (2020) [1] from the University of Melbourne –Australia published an interesting study about the immune response in a patient with mild-to-moderate COVID-19. The patient did not experience complications and she was recovered, probably due to her immune response (recruitment of immune cell populations, and IG- SARS-CoV-2-binding antibodies).

Supplements that may boost immune system defenses could be used to reduce the severity and risk of death from SARS-CoV-2 infection. Since COVID-19 pandemic occurred in winter, vitamin D deficiency may be involved in the worst prognosis observed in older patients [2]. Vitamin D deficiency in the elderly and especially in winter has been well documented. Both the innate and adaptive immune responses are modulated by vitamin D. During infection, vitamin D (through its receptor) modulates the function of both monocytes and macrophages, prevents infection-associated inflammatory response by inhibiting the maturation of dendritic cells [3], decreasing pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL-1β, and enhancing anti-inflammatory IL-10 [4]. In a meta-analysis including 25 trials and 11321 participants, it has been found that vitamin D supplementation significantly decreased the risk of acute respiratory tract infection (OR: 0.88, 95% CI: 0.81–0.96, p = 0.003). Interestingly, the most important benefit was attributed to persons with important vitamin D deficiency [5]. Likewise, vitamin D was found to prevent respiratory tract infections, mainly through stimulating the immune system [6]. Furthermore, vitamin D was shown to alleviate 21 types of adverse effects and synergize with 39 drugs, through its positive effects on the immune system and against the oxidative stress [7]. Immune responses can also be enhanced by vitamin C. Indeed, vitamin C supplementation enhanced the Th1 immune response in vitro [8]. An uncontrolled longitudinal clinical trial using vitamin C (500 mg) is ongoing in Palermo hospital –Italy (NCT04323514). In this trial, 500 patients with COVID-19 will receive 10 g of vitamin C intravenously in addition to conventional therapy. Another randomized clinical trial (NCT04264533) is conducted at Zhongnan Hospital in Wuhan, China, to evaluate the clinical efficacy and safety of intravenous vitamin C on coronavirus patients.

On the other hand, it should be noticed that a long-life correct nutrition and adequate vitamins levels are highly recommended for a healthy condition. A correct nutritional status, through anti-inflammatory nutrients may contribute to prevent different infectious and inflammatory diseases, such as COVID-19. Indeed, a poor nutritional status and especially vitamin deficiencies are considered a risk factor for a poor prognosis among COVID-19 patients [9]. Recently, we have asked for an urgent nutritional intervention model that should be established to prevent and/or minimize the negative effects of COVID-19 [10]. Furthermore, immunosupportive nutrients have been also recommended for healthy persons to alleviate the quarantine-related negative health effects [11].

Based on those precedents and given their wide therapeutic index, we suggest using vitamins D and C supplementation to enhance the immune system fitness to fight the SARS-CoV-2 infection. This vitamin supplementation requires assessing vitamin D status of the supplemented patients to avoid related negative effects.

Sources of financial support

None.

Funding

The authors report no funding.

Conflict of interest

No Conflict of interest to declare.

Acknowledgments

The authors have no acknowledgments.

References

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Thevarajan I , Nguyen T , Koutsakos M , Druce J , Caly L , van de Sandt CE , J, et al.. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nature Med. 2020;1–3. https://doi.org/10.1038/s41591-020-0819-2

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Zhang L , Liu Y . Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020;92(5):479–90. https://doi.org/10.1002/jmv.25707

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Jiménez-Sousa MÁ , Martínez I , Medrano LM , Fernández-Rodríguez A , Resino S . Vitamin D in Human Immunodeficiency Virus Infection: Influence on Immunity and Disease. Front Immunol. 2018;9:458. https://doi.org/10.3389/fimmu.2018.00458

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Hoe E , Nathanielsz J , Toh ZQ , Spry L , Marimla R , Balloch A , Mulholland K , Licciardi PV . Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection. Nutrients. 2016;8(12):806. https://doi.org/10.3390/nu8120806

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Martineau AR , Jolliffe DA , Hooper RL , Greenberg L , Aloia JF , Bergman P , Dubnov-Raz G , Esposito S , Ganmaa D , Ginde AA et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ.. 2017;356:i6583. https://doi.org/10.1136/bmj.i6583

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Charan J , Goyal JP , Saxena D , Yadav P . Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. J Pharmacol Pharmacother. 2012;3(4):300–3. https://doi.org/10.4103/0976-500X.103685

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Peng J , Liu Y , Xie J , Yang G , Huang Z . Effects of Vitamin D on drugs: Response and disposal. Nutrition. 2020;74:110734. https://doi.org/10.1016/j.nut.2020.110734

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Qin X , Liu J , Du Y , Li Y , Zheng L , Chen G , Cao Y . Different doses of vitamin C supplementation enhances the Th1 immune response to early Plasmodium yoelii 17XL infection in BALB/c mice. Int Immunopharmacol. 2019;70:387–95. https://doi.org/10.1016/j.intimp.2019.02.031

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Zabetakis I , Lordan R , Norton C , Tsoupras A . COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients. 2020;12:1466.

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Muscogiuri G , Barrea L , Savastano S , Colao A . Nutritional recommendations for CoVID-19 quarantine. Eur J Clin Nutr. . 2020;74:850–1.