Essential Immunonutrients in COVID-19: An Evidence-Based Review
Keywords:
Vitamin C, vitamin D, zinc, immunity, immunonutrition, COVID-19
Abstract
A ‘well-fed’ immune system is extremely important to ensure it performs the function of protecting against the viral offense. Various nutrients and minerals play a vital role in maintaining the integrity and function of the immune system. Among the various nutrients and minerals, vitamin C, vitamin D, and zinc stand out for having immune-modulatory functions which are demonstrated in a substantial body of evidence. In the ongoing pandemic of COVID-19, nutrients that can optimize the immune system to prevent or lower the risk of severe disease progression are very essential. Medical literature shows that deficiency of one or more of these nutrients may affect the immunity status of an individual and may predispose a person to an adverse prognosis of COVID-19. Therefore, adequate intake of vitamin C, D, and zinc may present as a promising tool in prehabilitation with immunonutrition for COVID-19 prevention and management. This review provides a comprehensive overview of the role of vitamin C, D, and zinc as an immunomodulatory agent in COVID-19 management.
Conflict of Interest: Dr. Manish Maladkar, Dr. Ashok Yadav and Nehali Save are employed by Aristo Pharmaceuticals Private Limited, India.
References
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26. Li YC. Vitamin D regulation of the renin–angiotensin system. Journal of cellular biochemistry. 2003;88(2):327-31.
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30. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.
31. Sharifi A, Vahedi H, Nedjat S, Rafiei H, Hosseinzadeh-Attar MJ. Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: A randomized placebo- controlled trial. APMIS. 2019; 127:681–687.
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PloS one. 2013;8(6):e65835.
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35. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta- analysis of individual participant data. BMJ. 2017;356.
36. Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebocontrolled, study (SHADE study). Postgraduate medical journal. Postgrad Med J 2020;0:1–4.
37. Saper RB, Rash R. Zinc: an essential micronutrient. American family physician. 2009;79(9):768.
38. Zinc Deficiency in Humans affecting Immune System [Internet]. [cited 2021 Jun 06]. Available from: https://indiacsr. in/zinc-deficiency-humans-affecting-immune-system/
39. Yanagisawa H. Zinc deficiency and clinical practice. Japan Medical Association Journal. 2004;47(8):359-64.
40. Chasapis CT, Ntoupa PS, Spiliopoulou CA, Stefanidou ME. Recent aspects of the effects of zinc on human health. Archives of toxicology. 2020;94:1443-60.
41. Prasad AS. Zinc in human health: effect of zinc on immune cells. Molecular medicine. 2008;14(5):353-7.
42. Berger A. What does zinc do? BMJ. 2002;325(7372):1062.
43. Skalny AV, Rink L, Ajsuvakova OP, Aschner M, Gritsenko VA, Alekseenko SI, et al. Zinc and respiratory tract infections: Perspectives for COVID‑19. International journal of molecular medicine. 2020;46(1):17-26.
44. Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. The American journal of clinical nutrition. 2007;85(3):837-44.
45. Johnstone J, Roth DE, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Cmaj.
2012;184(10):E551-61.
46. Carlucci P, Ahuja T, Petrilli CM, Rajagopalan H, Jones S, Rahimian J. Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients. MedRxiv. 2020.
47. Frontera JA, Rahimian JO, Yaghi S, Liu M, Lewis A, de Havenon A, et al. Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19
Patients: A Multi-Center Cohort Study. Res Sq [Preprint]. 2020;rs.3.rs-94509.
48. COVID-19 Treatment Guidelines [Internet]. [cited 2021 Jun 06]. Available from: https://www.covid19treatmentguidelines. nih.gov/supplements/zinc/
2. Lai CC, Shih TP, Ko WC, Tang HJ and Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic
and the challenges. International journal of antimicrobial agents. 2020;55(3), p.105924.
3. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health. 2020;13(11):1619-1629.
4. Maladkar M, Tekchandani MC, Karchodi MA. COVID-19 Treatment: Current and Emerging Options. The Indian Practitioner. 2020;73(6):37-41.
5. Yazdanpanah F, Hamblin MR, Rezaei N. The immune system and COVID-19: Friend or foe? Life Sci. 2020;256:117900.
6. Zhong J, Tang J, Ye C, Dong L. The immunology of COVID-19: is immune modulation an option for treatment? The Lancet Rheumatology. 2020;2(7):e428-e436.
7. Calder PC. Nutrition, immunity and COVID-19. BMJ Nutrition, Prevention & Health. 2020; 3(1), p.74.
8. Derbyshire E, Delange J. COVID-19: is there a role for immunonutrition, particularly in the over 65s? BMJ Nutrition, Prevention & Health. 2020;3(1):100.
9. Burns JJ,. Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid. Nature. 1957;180(4585):pp.553-553.
10. Schleicher RL, Carroll MD, Ford ES, and Lacher DA.. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES). The American journal of clinical nutrition. 2009;90(5): pp.1252-1263.
11. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999; 69(6):1086-107.
12. Maxfield L, Crane JS. Vitamin C Deficiency. [Updated 2020 Jul 2]. In: StatPearls [Internet]. [cited 2021 Jun 09] Available from: https://www.ncbi.nlm.nih.gov/books/NBK493187/
13. Carr AC and Maggini S. Vitamin C and immune function. Nutrients.2017; 9(11), p.1211.
14. Carr AC, Rowe S. The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19. Nutrients. 2020; 12(11):3286.
15. Holford P, Carr AC, Jovic TH, Ali SR, Whitaker IS, Marik PE, et al. Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients. 2020;12(12):3760.
16. Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. Journal of translational medicine. 2014; 12(1), pp.1-10.
17. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients.
Annals of surgery. 2002;236(6):814.
18. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest. 2017;151(6):1229-38.
19. Crimi E, Liguori A, Condorelli M, Cioffi M, Astuto M, Bontempo P, et al. The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: a
prospective, randomized, double-blind, placebo-controlled trial. Anesthesia & Analgesia. 2004;99(3):857-63.
20. Feyaerts AF and Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? Nutrition. 2020; 79, p.110948.
21. Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treat-ment and prevention. Rev Endocrine Metab Disord. 2017;18:153–65
22. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of infection and public health. 2020;13(10): 1373-1380
23. Grant WB, Al Anouti F, Moukayed M. Targeted 25- hydroxyvitamin D concentration measurements and vitamin D3 supplementation can have important patient and public
health benefits. Eur J Clin Nutr. 2020;74:366–76.
24. Sassi F, Tamone C and D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018;10(11), p.1656.
25. Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996;10(2):142-53.
26. Li YC. Vitamin D regulation of the renin–angiotensin system. Journal of cellular biochemistry. 2003;88(2):327-31.
27. Zittermann A, Gummert JF. Nonclassical vitamin D actions. Nutrients. 2010;2(4):408-25.
28. Lai YH, Fang TC. The pleiotropic effect of vitamin D. ISRN nephrology. 2013; Article ID 898125
29. Kalia V, Studzinski GP, Sarkar S. Role of vitamin D in regulating COVID‐19 severity—An immunological perspective. Journal of Leukocyte Biology. J Leukoc Biol. 2021;1–11
30. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.
31. Sharifi A, Vahedi H, Nedjat S, Rafiei H, Hosseinzadeh-Attar MJ. Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: A randomized placebo- controlled trial. APMIS. 2019; 127:681–687.
32. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988.
33. Bergman P, Lindh ÅU, Björkhem-Bergman L, Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials.
PloS one. 2013;8(6):e65835.
34. Charan J, Goyal JP, Saxena D, Yadav P. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. Journal of pharmacology & pharmacotherapeutics. 2012;3(4):300.
35. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta- analysis of individual participant data. BMJ. 2017;356.
36. Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebocontrolled, study (SHADE study). Postgraduate medical journal. Postgrad Med J 2020;0:1–4.
37. Saper RB, Rash R. Zinc: an essential micronutrient. American family physician. 2009;79(9):768.
38. Zinc Deficiency in Humans affecting Immune System [Internet]. [cited 2021 Jun 06]. Available from: https://indiacsr. in/zinc-deficiency-humans-affecting-immune-system/
39. Yanagisawa H. Zinc deficiency and clinical practice. Japan Medical Association Journal. 2004;47(8):359-64.
40. Chasapis CT, Ntoupa PS, Spiliopoulou CA, Stefanidou ME. Recent aspects of the effects of zinc on human health. Archives of toxicology. 2020;94:1443-60.
41. Prasad AS. Zinc in human health: effect of zinc on immune cells. Molecular medicine. 2008;14(5):353-7.
42. Berger A. What does zinc do? BMJ. 2002;325(7372):1062.
43. Skalny AV, Rink L, Ajsuvakova OP, Aschner M, Gritsenko VA, Alekseenko SI, et al. Zinc and respiratory tract infections: Perspectives for COVID‑19. International journal of molecular medicine. 2020;46(1):17-26.
44. Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. The American journal of clinical nutrition. 2007;85(3):837-44.
45. Johnstone J, Roth DE, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Cmaj.
2012;184(10):E551-61.
46. Carlucci P, Ahuja T, Petrilli CM, Rajagopalan H, Jones S, Rahimian J. Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients. MedRxiv. 2020.
47. Frontera JA, Rahimian JO, Yaghi S, Liu M, Lewis A, de Havenon A, et al. Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19
Patients: A Multi-Center Cohort Study. Res Sq [Preprint]. 2020;rs.3.rs-94509.
48. COVID-19 Treatment Guidelines [Internet]. [cited 2021 Jun 06]. Available from: https://www.covid19treatmentguidelines. nih.gov/supplements/zinc/
Published
2021-06-29
How to Cite
Dr. Manish Maladkar, Dr. Ashok Yadav, Nehali Save. (2021). Essential Immunonutrients in COVID-19: An Evidence-Based Review. The Indian Practitioner, 74(6), 20-26. Retrieved from https://articles.theindianpractitioner.com/index.php/tip/article/view/1192
Section
Review article
