Abstract. According to statistics, millions of people around the world have been infected with or are currently infected with the SARS-CoV-2 virus, which causes respiratory, cardiovascular, and urinary tract damage. It is known that vitamins D and C have immune-boosting properties that help protect the body against infection. Various studies have shown that a deficiency in these vitamins increases the risk and severity of the disease. This has drawn attention to the impact of vitamins on people infected with the SARS-CoV-2 virus. Vitamin D has been found to play a role in the production of protective peptides: β-defensins and cathelicidins, and modulates the activity of the renin-angiotensin-aldosterone system. β-defensins are responsible for perforating the virus capsid, while cathelicidins promote the dilation of blood vessel walls, which increases the influx of macrophages and their activation. Vitamin C, on the other hand, inhibits the activity of the cytokine storm that occurs as a result of hyperinflammation in affected areas of the body and also reduces the level of IL-6 and inhibits in vivo release of IL-6 in endothelium induced by endothelin-1 (ET-1). In this article, we review current research on the role of vitamins D and C in supporting immunity at various levels, particularly in the context of respiratory infections, with a focus on COVID-19. These levels include recovery and antibody production against the pathogen, infection prevention, easing of disease progression, supportive therapy, and the consequences of the disease. Although studies on the impact of calciferol and ascorbic acid on coronavirus progression are still ongoing, the results obtained indicate the potential usefulness of their use in the treatment of COVID-19.

Article received: 25.04.2023

Keywords: COVID-19, vitamin D, vitamin С, β-defensin, cathelicidins, cytokine storm, oxidative stress

Full text: PDF (Ukr)

1. 1. Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients. Switzerland; 2020;12(9).doi.org/10.3390/nu12092757
2. 2. D'Ecclesiis O, Gavioli C, Martinoli C, Raimondi S, Chiocca S, Miccolo C, et al. Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.PLoS One. United States; 2022;17(7):e0268396.doi.org/10.1371/journal.pone.0268396
3. 3. Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Netw open. United States; 2020;3(9):e2019722. doi.org/10.1001/jamanetworkopen.2020.19722
4. 4. Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One. United States; 2020;15(9):e0239252.doi.org/10.1371/journal.pone.0239252
5. 5. Saxena P, Nigam K, Mukherjee S, Chadha S, Sanyal S. Relation of vitamin D to COVID-19. J Virol Methods. Netherlands; 2022;301:114418.doi.org/10.1016/j.jviromet.2021.114418
6. 6. Maggini S, Maldonado P, Cardim P, Newball CF, Sota Latino ER. Vitamins C, D and Zinc: Synergistic Roles in Immune Function and Infections. Vitam Miner. 2017;06(03).doi.org/10.4172/2376-1318.1000167
7. 7. Encyclopedia TF, Free T. Cite This Page. 2023;11-3.
8. 8. Miner KT, Croft M. Generation, Persistence, and Modulation of Th0 E ector Cells: Role of Autocrine IL-4 and IFN-. 2017;1-9
9. 9. Bizuti MR, Starck É, da Silva Fagundes KK, Puhle JG, Lima LM, de Oliveira NR, et al. Influence of exercise and vitamin D on the immune system against Covid-19: an integrative review of current literature. Mol Cell Biochem. Netherlands; 2022;477(6):1725-37.doi.org/10.1007/s11010-022-04402-7
10. 10. Alberts B, Johnson A, Lewis J et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Helper T Cells and Lymphocyte Activation. Disponible: https://www.ncbi.nlm.nih.gov/books/NBK26827
11. 11. Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients. Aging Clin Exp Res. Germany; 2020;32(10):2141-58.doi.org/10.1007/s40520-020-01677-y
12. 12. Ristic-Medic D, Petrovic S, Arsic A, Vucic V. Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition. World J Gastroenterol. United States; 2021;27(34):5682-99.doi.org/10.3748/wjg.v27.i34.5682
13. 13. Luan Y-Y, Yin C-H, Yao Y-M. Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections. Front Immunol. Switzerland; 2021;12:720363.doi.org/10.3389/fimmu.2021.720363
14. 14. Kheiri B, Abdalla A, Osman M, Ahmed S, Hassan M, Bachuwa G. Vitamin D deficiency and risk of cardiovascular diseases: a narrative review. Clinical Hypertension; 2018;1-9.doi.org/10.1186/s40885-018-0094-4
15. 15. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D Deficiency and Risk of Cardiovascular Disease. 2008.doi.org/10.1161/CIRCULATIONAHA.107.706127
16. 16. Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. Germany; 2020;32(7):1195-8.doi.org/10.1007/s40520-020-01570-8
17. 17. Alberca GGF, Alberca RW. Role of vitamin D deficiency and comorbidities in COVID-19. World J Virol. United States; 2022;11(1):85-9.doi.org/10.5501/wjv.v11.i1.85
18. 18. Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int a J Establ as result Coop between Eur Found Osteoporos Natl Osteoporos Found USA. England; 2011;22(6):1745-53.doi.org/10.1007/s00198-010-1383-2
19. 19. Kim D-H, Meza CA, Clarke H, Kim J-S, Hickner RC. Vitamin D and Endothelial Function. Nutrients. Switzerland; 2020;12(2).doi.org/10.3390/nu12020575
20. 20. Progress M, Holick MF. Vitamin D Deficiency. 2007;266-81.doi.org/10.1056/NEJMra070553
21. 21. Daei Sorkhabi A, Sarkesh A, Daei Sorkhabi A, Entezari-Maleki T, Rashedi J, Bannazadeh Baghi H. Vitamin supplementation as a potential adjunctive therapeutic approach for COVID-19: biological and clinical plausibility. J Basic Clin Physiol Pharmacol. Germany; 2021;33(1):55-77.doi.org/10.1515/jbcpp-2021-0111
22. 22. Shahbaz U. Chitin, Characteristic, Sources, and Biomedical Application. Curr Pharm Biotechnol. Netherlands; 2020;21(14):1433-43.doi.org/10.2174/1389201021666200605104939
23. 23. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.
24. 24. Shahin MA, Khalil WA, Saadeldin IM, Swelum AA, El-Harairy MA. Effects of vitamin C, vitamin E, selenium, zinc, or their nanoparticles on camel epididymal spermatozoa stored at 4 °C. Trop Anim Health Prod. United States; 2021;53(1):86.doi.org/10.1007/s11250-020-02521-1
25. 25. Feyaerts AF, Luyten W. Vitamin C as prophylaxis and adjunctive medical treatment for COVID-19? Nutrition. United States; 2020;79-80:110948.doi.org/10.1016/j.nut.2020.110948
26. 26. Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open.England; 2020;10(7):e039519.doi.org/10.1136/bmjopen-2020-039519
27. 27. Poyton RO, Ball KA, Castello PR. Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab. United States; 2009;20(7):332-40.doi.org/10.1016/j.tem.2009.04.001
28. 28. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. United States; 2010;49(11):1603-16.doi.org/10.1016/j.freeradbiomed.2010.09.006
29. 29. Coussens LM, Werb Z. Inflammation and cancer. Nature. England; 2002;420(6917):860-7.doi.org/10.1038/nature01322
30. 30. Reid MB. Invited Review: redox modulation of skeletal muscle contraction: what we know and what we don't. J Appl Physiol. United States; 2001;90(2):724-31.doi.org/10.1152/jappl.2001.90.2.724
31. 31. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer. England;2003;3(4):276-85.doi.org/10.1038/nrc1046
32. 32. Zhang J-M, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. United States; 2007;45(2):27-37.doi.org/10.1097/AIA.0b013e318034194e
33. 33. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J cancer. United States; 2007;121(11):2381-6.doi.org/10.1002/ijc.23192
34. 34. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J cancer. United States; 2007;121(11):2373-80.doi.org/10.1002/ijc.23173
35. 35. Xiong-Pei Liang, Yi Li, Yin-Mei Hou, Hong Qiu Q-CZ. Effect of dietary vitamin C on the growth performance, antioxidant ability and innate immunity of juvenile yellow catfish (Pelteobagrus fulvidraco Richardson).
36. 36. Bagheri Hosseinabadi M, Khanjani N, Norouzi P, Faghihi-Zarandi A, Darban-Sarokhalil D, Khoramrooz SS, et al. The Effects of Antioxidant Vitamins on Proinflammatory Cytokines and Some Biochemical Parameters of Power Plant Workers: A Double-Blind Randomized Controlled Clinical Trial. Bioelectromagnetics. United States; 2021;42(1):18-26.doi.org/10.1002/bem.22294
37. 37. Yadav SS, Kumar R, Khare P, Tripathi M. Oxidative Stress Biomarkers in the Freshwater Fish, Heteropneustes fossilis (Bloch) Exposed to Sodium Fluoride: Antioxidant Defense and Role of Ascorbic Acid. Toxicol Int. India; 2015;22(1):71-6.doi.org/10.4103/0971-6580.172261
38. 38. Pons S, Fodil S, Azoulay E, Zafrani L. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Crit Care. England; 2020;24(1):353.doi.org/10.1186/s13054-020-03062-7
39. 39. Iddir M, Brito A, Dingeo G, Fernandez Del Campo SS, Samouda H, La Frano MR, et al. Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients. Switzerland; 2020;12(6).doi.org/10.3390/nu12061562
40. 40. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. United States; 2020;146(1):128-136.e4.doi.org/10.1016/j.jaci.2020.05.008
41. 41. Kang CK, Han G-C, Kim M, Kim G, Shin HM, Song K-H, et al. Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. Canada; 2020;97:313-21.doi.org/10.1016/j.ijid.2020.05.106
42. 42. Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, et al. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19? Maturitas. Ireland; 2021;143:1-9.doi.org/10.1016/j.maturitas.2020.08.003
43. 43. Milani GP, Macchi M, Guz-Mark A. Vitamin C in the Treatment of COVID-19. Nutrients. Switzerland; 2021;13(4).doi.org/10.3390/nu13041172
44. 44. Yaseen MO, Jamshaid H, Saif A, Hussain T. Immunomodulatory role and potential utility of various nutrients and dietary components in SARS-CoV-2 infection. Int J Vitam Nutr Res Int Zeitschrift fur Vitamin- und Ernahrungsforschung J Int Vitaminol Nutr. Switzerland;2022;92(1):35-48.doi.org/10.1024/0300-9831/a000715
45. 45. Canali R, Natarelli L, Leoni G, Azzini E, Comitato R, Sancak O, et al. Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects. Genes Nutr. Germany;2014;9(3):390.doi.org/10.1007/s12263-014-0390-x
46. 46. Goldstein S, Meyerstein D, Czapski G. The Fenton reagents. Free Radic Biol Med.Pergamon; 1993;15(4):435-45.doi.org/10.1016/0891-5849(93)90043-T
47. 47. Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo G, et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care. Germany; 2021;11(1):5.doi.org/10.1186/s13613-020-00792-3
48. 48. Carr AC, Rowe S. Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective. Nutrients. Switzerland; 2020;12(7).doi.org/10.3390/nu12071963
49. 49. Gao D, Xu M, Wang G, Lv J, Ma X, Guo Y, et al. The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study. Aging (Albany NY). United States; 2021;13(5):7020-34.doi.org/10.18632/aging.202557
50. 50. Kumari P, Dembra S, Dembra P, Bhawna F, Gul A, Ali B, et al. The Role of Vitamin C as Adjuvant Therapy in COVID-19. Cureus. United States; 2020;12(11):e11779.doi.org/10.7759/cureus.11779
51. 51. Al Sulaiman K, Aljuhani O, Saleh K Bin, Badreldin HA, Al Harthi A, Alenazi M, et al. Author Correction: Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study. Vol. 11, Scientific reports England; 2021. p. 19433.doi.org/10.1038/s41598-021-99146-7
52. 52. Yildirim F, Karaman I, Şimşek M. Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia. Vol. 159, Medicina clinica Spain; 2022. p. e25-6.doi.org/10.1016/j.medcli.2021.12.001
53. 53. Thomas S, Patel D, Bittel B, Wolski K, Wang Q, Kumar A, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw open. United States; 2021;4(2):e210369.doi.org/10.1001/jamanetworkopen.2021.0369
54. 54. Hernández A, Papadakos PJ, Torres A, González DA, Vives M, Ferrando C, et al. Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19. Rev Esp Anestesiol Reanim. Spain; 2020;67(5):245-52.doi.org/10.1016/j.redare.2020.05.002
55. 55. Honore PM, Blackman S, Bousbiat I, Perriens E, Attou R. Up to 100 g of Intravenous Vitamin C Appears to be Safe and Elicits No Adverse Effects but Needs Further Evaluation in High-Risk Groups. Clin Pharmacokinet. Switzerland; 2022;61(9):1199-202.doi.org/10.1007/s40262-022-01156-9
56. 56. Sahib HB, Kathum OA, Alanee RS, Jawad RAM, Al-Shammari AM. The Anti-Cytokine Storm Activity of Quercetin Zinc and Vitamin C Complex. Adv Virol. United States;2022;2022:1575605.doi.org/10.1155/2022/1575605
57. 57. Refat MS, Hamza RZ, Adam AMA, Saad HA, Gobouri AA, Al-Harbi FS, et al. Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies. PLoS One. United States; 2021;16(3):e0246265.doi.org/10.1371/journal.pone.0246265
58. 58. Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr. Springer US; 2020;74(11):1498-513.doi.org/10.1038/s41430-020-0558-y
59. 59. Carr AC, Rowe S. Factors affecting vitamin С status and prevalence of deficiency:A global health perspective. Nutrients. 2020;12(7):1-19.doi.org/10.3390/nu12071963