Vitamins and Minerals in Viral Infections: A Review Focusing on COVID-19

Abstract

The coronavirus disease 2019 (COVID-19), considered as a pandemic, has become an important threat to the health systems and economies of countries. Currently, there is no drug that can precisely prevent or treat this virus outbreak. Therefore, it is important to have a healthy immune system to prevent and manage the disease. Vitamins and minerals are important nutrients that play an active role in creating a healthy immune response and increasing the body's resistance to infections. Vitamins and minerals have various roles in the immune system regulation such as ensuring the development and differentiation of  macrophages, neutrophils and natural killer cells and regulation of T and B lymphocyte response. The potential role of these vitamins and minerals in the COVID-19 pandemic has begun to be widely discussed both in the literature and in the media. Therefore, in this review the role of vitamins and minerals in viral infections was investigated with a focus on COVID-19.

Keywords

• COVID-19
• Immune system
• Vitamins
• Minerals
• Nurition

Viral Enfeksiyonlarda Vitamin ve Mineraller: COVID-19 Odağında Bir Derleme

Abstract

Özet

Pandemi olarak kabul edilen koronavirüs hastalığı 2019 (COVID-19) ülkelerin sağlık sistemleri ve ekonomileri için önemli bir tehdit haline gelmiştir. Güncel durumda, bu virüs salgınını kesin olarak önleyebilen veya tedavi edebilen herhangi bir ilaç bulunmamaktadır. Bu nedenle, hastalıktan korunmak ve hastalığı yönetmek için sağlıklı bir bağışıklık sistemine sahip olmak önemlidir. Vitamin ve mineraller, sağlıklı bir bağışıklık yanıtının oluşturulmasında etkin rol oynayan ve vücudun enfeksiyonlara karşı olan direncini arttıran önemli besin ögeleridir. Vitamin ve minerallerin, makrofajlar, nötrofiller ve doğal öldürücü hücrelerin gelişiminin ve farklılaşmasının sağlanması, T ve B lenfosit yanıtının düzenlenmesi gibi bağışıklık sistemi üzerinde çeşitli etkileri mevcuttur. COVID-19 pandemisinde bu vitamin ve mineraller hem literatürde hem de medyada yaygın olarak tartışılmaya başlanmıştır. Bu nedenle, bu derlemede COVID-19 odağında viral enfeksiyonlarda vitamin ve minerallerin rolü incelenmiştir.

Anahtar Kelimeler: COVID-19, bağışıklık sistemi, vitaminler, mineraller, beslenme.

Abstract

The coronavirus disease 2019 (COVID-19), which is considered as a pandemic, has become an important threat to the health systems and economies of countries. Currently, there is no drug that can precisely treat this virus or prevent its outbreak. Thus, it is important to have a healthy immune system to prevent and manage the disease. Vitamins and minerals are important nutrients that play an active role in creating a healthy immune response and increasing the body’s resistance to infections. Vitamins and minerals have various impacts in the immune system regulation, such as ensuring the development and differentiation of macrophages, neutrophils, and natural killer cells, and regulating the T and B lymphocyte response. In the COVID-19 pandemic these vitamins and minerals has begun to be widely discussed both in the literature and in the media. Therefore, in this review, the role of vitamins and minerals in viral infections was investigated with a focus on COVID-19.

Keywords: COVID-19, immune system, vitamins, minerals, nutrition.

Keywords

• COVID-19
• Bağışıklık sistemi
• Vitaminler
• Mineraller
• Beslenme

References

1. Aibana, O., Franke, M., Huang, C. C., Galea, J., Calderón, R., Zhang, Z., et al. (2018). Vitamin E status is inversely associated with risk of incident tuberculosis disease among household contacts. The Journal of Nutrition, 148, 56-62.
2. Álvarez, R., Vaz, B., Gronemeyer, H., & de Lera Á. R. (2014). Functions, therapeutic applications, and synthesis of retinoids and carotenoids. Chemical Reviews, 114(1), 1-125.
3. Beard, J. A., Bearden, A., & Striker, R. (2011). Vitamin D and the anti-viral state. Journal of Clinical Virology, 50(3), 194-200.
4. Beck, M. A., Shi, Q., Morris, V. C., & Levander, O. A. (1995). Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nature Medicine, 1(5), 433-6.
5. Beck, M. A., Kolbeck, P. C., Rohr, L. H., Shi, Q., Morris, V. C., & Levander, O. A. (1994). Benign human enterovirus becomes virulent in selenium-deficient mice. Journal of Medical Virology, 43(2), 166-70.
6. Beck, M. A., Nelson, H. K., Shi, Q., Van Dael, P., Schiffrin, E. J., Blum, S., et al. (2001). Selenium deficiency increases the pathology of an influenza virus infection. The FASEB Journal, 15(8), 1481-3.
7. Broome, C. S., McArdle, F., Kyle, J. A., Andrews, F., Lowe, N. M., Hart, C. A., et al. (2004). An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. The American Journal of Clinical Nutrition, 80(1), 154-62.
8. Carr, A. C., & Maggini, S. (2017). Vitamin C and immune function. Nutrients, 9(11), 1211.

9. Chang, A. B., Torzillo, P. J., Boyce, N. C., White, A. V., Stewart, P. M., Wheaton, G. R., et al. (2006). Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: A randomised controlled trial. The Medical Journal of Australia, 184(3), 107-12.
10. Cheng, R. Z. (2020). Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Medicine in Drug Discovery, 5, 100028.
11. ClinicalTrials.gov Identifier: NCT04323514. (2020). Use ofascorbic acid in patients with COVID 19. Retrieved May 22, 2020, from https://clinicaltrials.gov/ct2/show/ NCT04323514
12. ClinicalTrials.gov Identifier: NCT04342728. (2020). Coronavirus 2019 (COVID-19)- Using ascorbic acid and zinc supplementation (COVIDAtoZ). Retrieved May 22, 2020, from https://clinicaltrials.gov/ct2/show/NCT04342728
13. ClinicalTrials.gov Identifier: NCT04344041. (2020). COVID-19 and vitamin D supplementation: a multicenter randomized controlled trial of high dose versus standard dose vitamin D3 in high-risk COVID-19 patients (CoVitTrial). Retrieved May 22, 2020, from https:// clinicaltrials.gov/ct2/show/NCT04344041
14. ClinicalTrials.gov Identifier: NCT04351490. (2020). Impact of zinc and vitamin D3 supplementation on the survival of aged patients infected with COVID-19 (ZnD3-CoVici). Retrieved May 22, 2020, from https://clinicaltrials.gov/ ct2/show/NCT04351490
15. ClinicalTrials.gov Identifier: NCT04357782. (2020). Administration of intravenous vitamin C in novel coronavirus infection and decreased oxygenation (AVoCaDO). Retrieved May 23, 2020, from https:// clinicaltrials.gov/ct2/show/NCT04357782
16. ClinicalTrials.gov Identifier: NCT04377646. (2020). A study of hydroxychloroquine and zinc in the prevention of COVID-19 infection in military healthcare workers (COVID-Milit). Retrieved May 24, 2020, from https:// clinicaltrials.gov/ct2/show/NCT04377646
17. Coperchini, F., Chiovato, L., Croce, L., Magri, F., & Rotondi, M. (2020). The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine & Growth Factor Reviews, 53, 25–32.
18. Dalamaga, M., Karampela, I., & Mantzoros, C. S. (2020). Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 treatment regimens? Metabolism Clinical and Experimental, 108, 154260.
19. Dancer, R. C. A., Parekh, D., Lax, S., D’Souza, V., Zheng, S., Bassford, C. R., et al. (2015). Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax, 70(7), 617-24.
20. D’Avolio, A., Avataneo, V., Manca, A., Cusato, J., De Nicolo, A., Lucchini, R., et al. (2020). 25-hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients, 12(5), 1359.
21. De la Fuente, M., Hernanz, A., Guayerbas, N., Victor, V. M., & Arnalich, F. (2008). Vitamin E ingestion improves several immune functions in elderly men and women. Free Radical Research, 42(3), 272-80.
22. Dowling, J. E. (2020). Vitamin A: Its many roles-from vision and synaptic plasticity to infant mortality. Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology, 206(3), 389-99.
23. Drakesmith, H., & Mulberg, A. (2008). Viral infection and iron metabolism. Nature Reviews Microbiology, 6, 541-52.
24. Forum of International Respiratory Societies. (2017). The global impact of respiratory disease. Second Edition. Sheffield, European Respiratory Society.
25. Galli, F., Azzi, A., Birringer, M., Cook-Mills, J. M., Eggersdorfer, M., Frank, J., et al. (2017). Vitamin E: Emerging aspects and new directions. Free Radical Biology & Medicine, 102, 16-36.
26. Ganz, T. (2018). Iron and infection. International Journal of Hematology, 107(1), 7-15.
27. Gasmi, A., Noor, S., Tippairote, T., Dadar, M., Menzel, A., & Bjorklund, G. (2020). Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic. Clinical Immunology, 215: 108409.
28. Graat, J. M., Schouten, E. G., & Kok, F. J. (2002). Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: A randomized controlled trial. The journal of the American Medical Association, 288(6), 715-21.
29. Grant, W. B., Lahore, H., McDonnell, S. L., Baggerly, C. A., French, C. B., Aliano, J. L., et al. (2020). Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 12(4), 988.
30. Guillin, O. M., Vindry, C., Ohlmann, T., & Chavatte, L. (2019). Selenium, selenoproteins and viral infection. Nutrients, 11(9), 2101.
31. Hastie, C. E., Mackay, D. F., Ho, F., Celis-Morales, C. A., Katikireddi, S. V., Niedzwiedz, C. L., et al. (2020). Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(4), 561-5.
32. Hemilä, H. (2016). Vitamin E administration may decrease the incidence of pneumonia in elderly males. Clinical Interventions in Aging, 11, 1379-85.
33. Hemilä, H., & Chalker, E. (2013). Vitamin C for preventing and treating the common cold. The Cochrane Database of Systematic Reviews, CD000980.
34. Hemilä, H., & Kaprio, J. (2008a). Vitamin E supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C. Nutrition Journal, 7, 33.
35. Hemilä, H., & Kaprio, J. (2008b). Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake. The British Journal of Nutrition, 100(4), 896-902.
36. Hemilä, H., Virtamo, J., Albanes, D., & Kaprio, J. (2006). The effect of vitamin E on common cold incidence is modified by age, smoking and residential neighborhood. Journal of the American College of Nutrition, 25, 332-9.
37. Huang, Z., Liu, Y., Qi, G., Brand, D., & Zheng, S. G. (2018). Role of vitamin A in the immune system. Journal of Clinical Medicine, 7(9), 258.
38. Ivory, K., Prieto, E., Spinks, C., Armah, C. N., Goldson, A. J., Dainty, J. R., et al. (2017). Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults. Clinical Nutrition, 36(2), 407-15.
39. Jayawardena, R., Sooriyaarachchi, P., Chourdakis, M., Jeewandara, C., & Ranasinghe, P. (2020). Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes and Metabolic Syndrome, 14(4), 367-82.
40. Khadangi, F., & Azzi, A. (2019). Vitamin E- The next 100 years. International Union of Biochemistry and Molecular Biology Life, 71(4), 411-5.
41. Lee, G. Y., & Han, S. N. (2018). The role of vitamin E in immunity. Nutrients, 10(11), 1614.
42. Li, C., Li, Y., & Ding, C. (2019). The role of copper homeostasis at the host-pathogen axis: From bacteria to fungi. International Journal of Molecular Sciences, 20(1), 175.
43. Liu, W., Zhang, S., Nekhai, S., & Liu, S. (2020). Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Current Clinical Microbiology Reports, 7, 13-9.
44. Maares, M., & Haase, H. (2016). Zinc and immunity: An essential interrelation. Archives of Biochemistry and Biophysics, 611, 58-65.
45. Maggini, S., Pierre, A., & Calder, P. C. (2018). Immune function and micronutrient requirements change over the life course. Nutrients, 10(10), 1531.
46. Mansur, J. (2020). Low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity [Letter to the editors]. Alimentary Pharmacology and Therapeutics.
47. Marko, M. G., Ahmed, T., Bunnell, S. C., Wu, D., Chung, H., Huber, B. T., et al. (2007). Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. The Journal of Immunology, 178(3), 1443-9.
48. Martineau, A. R., Jolliffe, D. A., Hooper, R. L., Greenberg, L., Aloia, J. F., Bergman, P., et al. (2017). Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. British Medical Journal, 356, i6583.
49. Mehta, P., McAuley, D., Brown, M., Sanchez, E., Tattersall, R., & Manson, J. (2020). COVID-19: Consider cytokine storm syndromes and immunosuppression. The Lancet, 395,1033-4.
50. Meydani, S. N., Leka, L. S., Fine, B. C., Dallal, G. E., Keusch, G. T., Singh, M. F., et al. (2004). Vitamin E and respiratory tract infections in elderly nursing home residents: A randomized controlled trial. Journal of the American Medical Association, 292(7), 828-36.
51. Meydani, S. N., Lewis, E. D., & Wu, D. (2018). Perspective: Should vitamin E recommendations for older adults be increased? Advances in Nutrition, 9(5), 533-43.
52. Olofin, I. O., Spiegelman, D., Aboud, S., Duggan, C., Danaei, G., & Fawzi, W. W. (2014). Supplementation with multivitamins and vitamin A and incidence of malaria among HIVinfected Tanzanian women. Journal of Acquired Immune Deficiency Syndromes, 67(4), 173-8.
53. Ortaç Ersoy, E. O., Tanriover, M. D., Ocal, S., Ozisik, L., Inkaya, C., & Topeli, A. (2016). Severe measles pneumonia in adults with respiratory failure: Role of ribavirin and high-dose vitamin A. The Clinical Respiratory Journal, 10(5), 673-5.
54. Panarese, A., & Shahini, E. (2020). Letter: Covid-19, and vitamin D [Letter to the editors]. Alimentary Pharmacology & Therapeutics, 9, 1-3.
55. Patel, N., Penkert, R. R., Jones, B. G., Sealy, R. E., Surman, S. L., Sun, Y., et al. (2019). Baseline serum vitamin A and D levels determine benefit of oral vitamin A&D supplements to humoral immune responses following pediatric influenza vaccination. Viruses, 11(10), 907.
56. Prasad, A. S. (2020). Lessons learned from experimental human model of zinc deficiency. Journal of Immunology Research, 2020, 9207279.
57. Qi, Y. J., Niu, Q. L., Zhu, X. L., Zhao, X. Z., Yang, W. W., & Wang, X. J. (2016). Relationship between deficiencies in vitamin A and E and occurrence of infectious diseases among children. European Review for Medical and Pharmacological Sciences, 20(23), 5009-12.
58. Quiros Roldan, E., Biasiotto, G., Magro, P., & Zanella, I. (2020). The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Pharmacological Research, 158, 104904.
59. Raha, S., Mallick, R., Basak, S., & Duttaroy, A. K. (2020). Is copper beneficial for COVID-19 patients? Medical Hypotheses, 142, 109814.
60. Rayman, M. P. (2012). Selenium and human health. The Lancet, 379 (9822), 1256-68.
61. Read, S. A., Obeid, S., Ahlenstiel, C., & Ahlenstiel, G. (2019). The role of zinc in antiviral immunity. Advances in Nutrition, 10(4), 696-710.
62. Rhodes, J. M., Subramanian, S., Laird, E., & Kenny, R. A. (2020). Editorial: Low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Alimentary Pharmacology and Therapeutics, 51(12), 1434-7. Rondanelli, M., Miccono, A., Lamburghini, S., Avanzato, I., Riva,
63. A., Allegrini, P., et al. (2018). Self-care for common colds: the pivotal role of vitamin D, vitamin C, zinc, and echinacea in three main immune interactive clusters (physical barriers, innate and adaptive immunity) involved during an episode of common colds-practical advice on dosages and on the time to take these nutrients/botanicals in order to prevent or treat common colds. Evidence Based Complementary and Alternative Medicine, 5813095.
64. Roy, S., & Awasthi, A. (2019). Vitamin A and the immune system. In Mahmoudi, M. & Rezaei, N. (Eds.), Cognition: Nutrition and immunity (pp. 53-73). Springer Nature Switzerland AG 2019.
65. Rupp, J. C., Locatelli, M., Grieser, A., Ramos, A., Campbell, P. J., Yi, H., et al. (2017). Host cell copper transporters CTR1 and ATP7A are important for influenza A virus replication. Virology Journal, 14(1), 11.
66. Sassi, F., Tamone, C., & D’Amelio, P. (2018). Vitamin D: Nutrient, hormone, and immunomodulator. Nutrients, 10(11). 1656.
67. Schoeman, D., & Fielding, B. C. (2019). Coronavirus envelope protein: current knowledge. Virology Journal 16(1), 69.
68. Science, M., Johnstone, J., Roth, D. E., Guyatt, G., & Loeb, M. (2012). Zinc for the treatment of the common cold: A systematic review and meta-analysis of randomized controlled trials. Canadian Medical Association Journal, 184(10), 551-61.
69. Shittu, M. O., & Afolami, O. I. (2020). Improving the efficacy of chloroquine and hydroxychloroquine against SARS-CoV-2 may require zinc additives - A better synergy for future COVID-19 clinical trials. Le Infezioni in Medicina, 2, 192-7.
70. Skalny, A. V., Rink, L., Ajsuvakova, O. P., Aschner, M., Gritsenko, V. A., Alekseenko, S. I., et al. (2020). Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review). International Journal of Molecular Medicine, 46, 17-26.
71. te Velthuis, A. J. W., van den Worm, S. H. E., Sims, A. C., Baric, R. S., Snijder, E. J., & van Hemert, M. J. (2010). Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLOS Pathogens, 6(11), e1001176.
72. Tenforde, M. W., Yadav, A., Dowdy, D. W., Gupte, N., Shivakoti, R., Yang, W. T., et al. (2017). Vitamin A and D deficiencies associated with incident Tuberculosis in HIV-infected patients initiating antiretroviral therapy in multinational case-cohort study. Journal of Acquired Immune Deficiency Syndromes, 75(3), 71-9.
73. Tian, Y., & Rong, L. (2020). Does vitamin D have a potential role against COVID-19? Authors’ reply [Letter to the editors]. Alimentary Pharmacology and Therapeutics.
74. Türkiye Beslenme Rehberi (TÜBER). (2015). T.C Sağlık Bakanlığı Yayın No:1031, Ankara 2016.
75. Turnlund, J. R., Jacob, R. A., Keen, C. L., Strain, J., Kelley, D. S., Domek, J. M., et al. (2004). Long-term high copper intake: Effects on indexes of copper status, antioxidant status, and immune function in young men. The American Journal of Clinical Nutrition, 79(6), 1037-44.
76. van Schoor, N., & Lips, P. (2017). Global overview of vitamin D status. Endocrinology and Metabolism Clinics of North America, 46(4), 845-70.
77. Warnes, S. L., Little, Z. R., & Keevil, C. W. (2015). Human coronavirus 229E remains infectious on common touch surface materials. mBio, 6(6), e01697-01615.
78. Weiss, G., & Carver, P. L. (2018). Role of divalent metals in infectious disease susceptibility and outcome. Clinical Microbiology and Infection, 24(1), 16-23.
79. Wessling-Resnick, M. (2018). Crossing the iron gate: Why and how transferrin receptors mediate viral entry. Annual Review of Nutrition, 38, 431-58.
80. West, C. E., Sijtsma, S. R., Kouwenhoven, B., Rombout, J. H., & van der Zijpp, A. J. (1992). Epithelia-damaging virus infections affect vitamin A status in chickens. The Journal of Nutrition,122(2), 333-9.
81. Wilson, M. E., Imdad, A., Herzer, K., Yakoob, M. Y., & Bhutta, Z. A. (2011). Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: Systematic review and meta-analysis. British Medical Journal, 343, d5094.
82. World Health Organization (WHO). (2018). Influenza (Seasonal). Retrieved May 20, 2020, from https://www.who.int/newsroom/ fact-sheets/detail/influenza-(seasonal)
83. Zhang, J., Sun, R. R., Yan, Z. X., Yi, W. X., & Yue, B. (2019). Correlation of serum vitamin A, D, and E with recurrent respiratory infection in children. European Review for Medical and Pharmacological Sciences, 23(18), 8133-8.
84. Zhang, J., Taylor, E. W., Bennett, K., Saad, R., & Rayman, M. P. (2020). Association between regional selenium status and reported outcome of COVID-19 cases in China [Letter to the editors]. The American Journal of Clinical Nutrition, 111(6), 1297–9.
85. Zhang, L., & Liu, Y. (2020). Potential interventions for novel coronavirus in China: A systematic review. Journal of Medical Virology, 92(5), 479-90.