Nutrition Research and Practice

한국영양학회 (The Korean Nutrition Society)
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Nutrient modulation of viral infection-implications for COVID-19

  • Kim, Hye-Keong (Department of Food Science and Nutrition, The Catholic University of Korea) ;
  • Park, Chan Yoon (Department of Food and Nutrition, College of Health Science, The University of Suwon) ;
  • Han, Sung Nim (Department of Food and Nutrition, College of Human Ecology, Seoul National University)
  • 투고 : 2021.04.01
  • 심사 : 2021.06.16
  • 발행 : 2021.12.01
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초록

The coronavirus disease 2019 (COVID-19) pandemic has put focus on the importance of a healthy immune system for recovery from infection and effective response to vaccination. Several nutrients have been under attention because their nutritional statuses showed associations with the incidence or severity of COVID-19 or because they affect several aspects of immune function. Nutritional status, immune function, and viral infection are closely interrelated. Undernutrition impairs immune function, which can lead to increased susceptibility to viral infection, while viral infection itself can result in changes in nutritional status. Here, we review the roles of vitamins A, C, D, and E, and zinc, iron, and selenium in immune function and viral infection and their relevance to COVID-19.

키워드

과제정보

This research was supported by grants from (National Research Foundation [NRF] of Korea [funding number: NRF-2021R1A2C2012013]) and supported by the Catholic University of Korea, Research Fund, 2021.

참고문헌

  1. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA 2020;324:782-93. https://doi.org/10.1001/jama.2020.12839
  2. Tay MZ, Poh CM, Renia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020;20:363-74. https://doi.org/10.1038/s41577-020-0311-8
  3. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-32. https://doi.org/10.1038/s41591-020-0968-3
  4. Sidor A, Rzymski P. Dietary choices and habits during COVID-19 lockdown: experience from Poland. Nutrients 2020;12:1657. https://doi.org/10.3390/nu12061657
  5. Rodriguez-Perez C, Molina-Montes E, Verardo V, Artacho R, Garcia-Villanova B, Guerra-Hernandez EJ, Ruiz-Lopez MD. Changes in dietary behaviours during the COVID-19 outbreak confinement in the Spanish COVIDiet study. Nutrients 2020;12:1730. https://doi.org/10.3390/nu12061730
  6. Hennet T, Peterhans E, Stocker R. Alterations in antioxidant defences in lung and liver of mice infected with influenza A virus. J Gen Virol 1992;73:39-46. https://doi.org/10.1099/0022-1317-73-1-39
  7. Meisel E, Efros O, Bleier J, Beit Halevi T, Segal G, Rahav G, Leibowitz A, Grossman E. Folate levels in patients hospitalized with coronavirus disease 2019. Nutrients 2021;13:812. https://doi.org/10.3390/nu13030812
  8. D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolo A, Lucchini R, Keller F, Cantu M. 25-Hydroxyvitamin d concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients 2020;12:1359. https://doi.org/10.3390/nu12051359
  9. Im JH, Je YS, Baek J, Chung MH, Kwon HY, Lee JS. Nutritional status of patients with COVID-19. Int J Infect Dis 2020;100:390-3. https://doi.org/10.1016/j.ijid.2020.08.018
  10. Carr AC, Maggini S. Vitamin C and immune function. Nutrients 2017;9:1211. https://doi.org/10.3390/nu9111211
  11. Mohammed BM, Fisher BJ, Kraskauskas D, Ward S, Wayne JS, Brophy DF, Fowler AA 3rd, Yager DR, Natarajan R. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J 2016;13:572-84. https://doi.org/10.1111/iwj.12484
  12. Huijskens MJ, Walczak M, Sarkar S, Atrafi F, Senden-Gijsbers BL, Tilanus MG, Bos GM, Wieten L, Germeraad WT. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy 2015;17:613-20. https://doi.org/10.1016/j.jcyt.2015.01.004
  13. Uchio R, Hirose Y, Murosaki S, Yamamoto Y, Ishigami A. High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice. Br J Nutr 2015;113:603-9. https://doi.org/10.1017/S0007114514003857
  14. Hemila H. Vitamin C and infections. Nutrients 2017;9:339. https://doi.org/10.3390/nu9040339
  15. Kim Y, Kim H, Bae S, Choi J, Lim SY, Lee N, Kong JM, Hwang YI, Kang JS, Lee WJ. Vitamin C is an essential factor on the anti-viral immune responses through the production of interferon-α/β at the initial stage of influenza A virus (H3N2) infection. Immune Netw 2013;13:70-4. https://doi.org/10.4110/in.2013.13.2.70
  16. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013:CD000980.
  17. Ran L, Zhao W, Wang J, Wang H, Zhao Y, Tseng Y, Bu H. Extra dose of vitamin C based on a daily supplementation shortens the common cold: a meta-analysis of 9 randomized controlled trials. BioMed Res Int 2018;2018:1837634. https://doi.org/10.1155/2018/1837634
  18. Jovic TH, Ali SR, Ibrahim N, Jessop ZM, Tarassoli SP, Dobbs TD, Holford P, Thornton CA, Whitaker IS. Could vitamins help in the fight against COVID-19? Nutrients 2020;12:2550. https://doi.org/10.3390/nu12092550
  19. Mohammed BM, Fisher BJ, Kraskauskas D, Farkas D, Brophy DF, Fowler AA 3rd, Natarajan R. Vitamin C: a novel regulator of neutrophil extracellular trap formation. Nutrients 2013;5:3131-51. https://doi.org/10.3390/nu5083131
  20. Erol N, Saglam L, Saglam YS, Erol HS, Altun S, Aktas MS, Halici MB. The protection potential of antioxidant vitamins against acute respiratory distress syndrome: a rat trial. Inflammation 2019;42:1585-94. https://doi.org/10.1007/s10753-019-01020-2
  21. Hemila H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis. Nutrients 2019;11:708. https://doi.org/10.3390/nu11040708
  22. Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko A, Halquist M. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA 2019;322:1261-70. https://doi.org/10.1001/jama.2019.11825
  23. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4. https://doi.org/10.1016/s0140-6736(20)30628-0
  24. U.S. National Library of Medicine. ClinicalTrials [Internet]. Bethesda (MD): U.S. National Library of Medicine; 2020 [cited 2020 October 13]. Available from: https://clinicaltrials.gov/ct2/results?term=vitamin+C+and+COVID19&Search=Search.
  25. Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition 2020;12:100190. https://doi.org/10.1016/j.phanu.2020.100190
  26. Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press; 2011.
  27. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 1983;57:1308-10. https://doi.org/10.1210/jcem-57-6-1308
  28. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 1983;221:1181-3. https://doi.org/10.1126/science.6310748
  29. Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 2008;8:685-98. https://doi.org/10.1038/nri2378
  30. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783-801. https://doi.org/10.1016/j.cell.2006.02.015
  31. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004;173:2909-12. https://doi.org/10.4049/jimmunol.173.5.2909
  32. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 2009;182:4289-95. https://doi.org/10.4049/jimmunol.0803736
  33. Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, Helfrich YR, Kang S, Elalieh HZ, Steinmeyer A, Zugel U, Bikle DD, Modlin RL, Gallo RL. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 2007;117:803-11. https://doi.org/10.1172/JCI30142
  34. Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H, Ylikomi T. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 2007;86:714-7. https://doi.org/10.1093/ajcn/86.3.714
  35. Roth DE, Shah R, Black RE, Baqui AH. Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr 2010;99:389-93. https://doi.org/10.1111/j.1651-2227.2009.01594.x
  36. Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr 2004;58:563-7. https://doi.org/10.1038/sj.ejcn.1601845
  37. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009;169:384-90. https://doi.org/10.1001/archinternmed.2008.560
  38. Bergman P, Lindh AU, Bjorkhem-Bergman L, Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLoS One 2013;8:e65835. https://doi.org/10.1371/journal.pone.0065835
  39. McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol 2009;44:981-8. https://doi.org/10.1002/ppul.21089
  40. Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O'Donnell CA, Gill JM, Sattar N, Pell JP. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 2020;14:561-5. https://doi.org/10.1016/j.dsx.2020.04.050
  41. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health 2020;13:1373-80. https://doi.org/10.1016/j.jiph.2020.06.021
  42. 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 2020;32:1195-8. https://doi.org/10.1007/s40520-020-01570-8
  43. Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One 2020;15:e0239252. https://doi.org/10.1371/journal.pone.0239252
  44. Mok CK, Ng YL, Ahidjo BA, Hua Lee RC, Choy Loe MW, Liu J, Tan KS, Kaur P, Chng WJ, Wong EL, Wang DY, Hao E, Hou X, Tan YW, Mak TM, Lin C, Lin R, Tambyah P, Deng J, Chu JJH. Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis. bioRxiv. Forthcoming 2020. CROSSREF
  45. Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of vitamin A in the immune system. J Clin Med 2018;7:258. https://doi.org/10.3390/jcm7090258
  46. Imdad A, Mayo-Wilson E, Herzer K, Bhutta ZA. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev 2017;3:CD008524.
  47. Liang Y, Yi P, Wang X, Zhang B, Jie Z, Soong L, Sun J. Retinoic acid modulates hyperactive T cell responses and protects vitamin A-deficient mice against persistent lymphocytic choriomeningitis virus infection. J Immunol 2020;204:2984-94. https://doi.org/10.4049/jimmunol.1901091
  48. Penkert RR, Smith AP, Hrincius ER, McCullers JA, Vogel P, Smith AM, Hurwitz JL. Effect of vitamin A deficiency in dysregulating immune responses to influenza virus and increasing mortality rates after bacterial coinfections. J Infect Dis 2021;223:1806-16. https://doi.org/10.1093/infdis/jiaa597
  49. Stephensen CB, Lietz G. Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2. Br J Nutr 2021:1-10.
  50. Lee GY, Han SN. The role of vitamin E in immunity. Nutrients 2018;10:1614. https://doi.org/10.3390/nu10111614
  51. Pae M, Wu D. Nutritional modulation of age-related changes in the immune system and risk of infection. Nutr Res 2017;41:14-35. https://doi.org/10.1016/j.nutres.2017.02.001
  52. Marko MG, Ahmed T, Bunnell SC, Wu D, Chung H, Huber BT, Meydani SN. Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. J Immunol 2007;178:1443-9. https://doi.org/10.4049/jimmunol.178.3.1443
  53. Marko MG, Pang HJ, Ren Z, Azzi A, Huber BT, Bunnell SC, Meydani SN. Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice. J Nutr 2009;139:1192-7. https://doi.org/10.3945/jn.108.103416
  54. Han SN, Wu D, Ha WK, Beharka A, Smith DE, Bender BS, Meydani SN. Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus. Immunology 2000;100:487-93. https://doi.org/10.1046/j.1365-2567.2000.00070.x
  55. Erol SA, Tanacan A, Anuk AT, Tokalioglu EO, Biriken D, Keskin HL, Moraloglu OT, Yazihan N, Sahin D. Evaluation of maternal serum afamin and vitamin E levels in pregnant women with COVID-19 and its association with composite adverse perinatal outcomes. J Med Virol 2021;93:2350-8. https://doi.org/10.1002/jmv.26725
  56. Prasad AS. Discovery of human zinc deficiency: 50 years later. J Trace Elem Med Biol 2012;26:66-9. https://doi.org/10.1016/j.jtemb.2012.04.004
  57. Lonnerdal B. Dietary factors influencing zinc absorption. J Nutr 2000;130:1378S-1383S. https://doi.org/10.1093/jn/130.5.1378S
  58. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med 2008;14:353-7. https://doi.org/10.2119/2008-00033.Prasad
  59. World Health Organization. The World Health report 2002. Midwifery 2003;19:72-3. https://doi.org/10.1054/midw.2002.0343
  60. Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O'Brien KL, Campbell H, Black RE. Global burden of childhood pneumonia and diarrhoea. Lancet 2013;381:1405-16. https://doi.org/10.1016/S0140-6736(13)60222-6
  61. Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003) 2004;44:594-603. https://doi.org/10.1331/1544-3191.44.5.594.Hulisz
  62. Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp (Warsz) 2008;56:15-30. https://doi.org/10.1007/s00005-008-0003-8
  63. Lazarczyk M, Favre M. Role of Zn2+ ions in host-virus interactions. J Virol 2008;82:11486-94. https://doi.org/10.1128/JVI.01314-08
  64. Uchide N, Ohyama K, Bessho T, Yuan B, Yamakawa T. Effect of antioxidants on apoptosis induced by influenza virus infection: inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate. Antiviral Res 2002;56:207-17. https://doi.org/10.1016/S0166-3542(02)00109-2
  65. Gaudernak E, Seipelt J, Triendl A, Grassauer A, Kuechler E. Antiviral effects of pyrrolidine dithiocarbamate on human rhinoviruses. J Virol 2002;76:6004-15. https://doi.org/10.1128/JVI.76.12.6004-6015.2002
  66. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 2010;6:e1001176. https://doi.org/10.1371/journal.ppat.1001176
  67. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One 2014;9:e109180. https://doi.org/10.1371/journal.pone.0109180
  68. Wessels I, Rolles B, Rink L. The potential impact of zinc supplementation on COVID-19 pathogenesis. Front Immunol 2020;11:1712. https://doi.org/10.3389/fimmu.2020.01712
  69. Skalny AV, Rink L, Ajsuvakova OP, Aschner M, Gritsenko VA, Alekseenko SI, Svistunov AA, Petrakis D, Spandidos DA, Aaseth J, Tsatsakis A, Tinkov AA. Zinc and respiratory tract infections: perspectives for COVID-19 (review). Int J Mol Med 2020;46:17-26.
  70. Zalewski PD, Truong-Tran AQ, Grosser D, Jayaram L, Murgia C, Ruffin RE. Zinc metabolism in airway epithelium and airway inflammation: basic mechanisms and clinical targets. A review. Pharmacol Ther 2005;105:127-49. https://doi.org/10.1016/j.pharmthera.2004.09.004
  71. Jothimani D, Kailasam E, Danielraj S, Nallathambi B, Ramachandran H, Sekar P, Manoharan S, Ramani V, Narasimhan G, Kaliamoorthy I, Rela M. COVID-19: poor outcomes in patients with zinc deficiency. Int J Infect Dis 2020;100:343-9. https://doi.org/10.1016/j.ijid.2020.09.014
  72. Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, Jurado J, Della Penna N, Celi LA. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest 2021;159:108-11. https://doi.org/10.1016/j.chest.2020.06.082
  73. Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr 2001;131:616S-633S. https://doi.org/10.1093/jn/131.2.616S
  74. Brock JH, Mulero V. Cellular and molecular aspects of iron and immune function. Proc Nutr Soc 2000;59:537-40. https://doi.org/10.1017/S002966510000077X
  75. Dhur A, Galan P, Hannoun C, Huot K, Hercberg S. Effects of iron deficiency upon the antibody response to influenza virus in rats. J Nutr Biochem 1990;1:629-34. https://doi.org/10.1016/0955-2863(90)90021-C
  76. Zhou C, Chen Y, Ji Y, He X, Xue D. Increased serum levels of hepcidin and ferritin are associated with severity of COVID-19. Med Sci Monit 2020;26:e926178.
  77. Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica 2020;105:260-72. https://doi.org/10.3324/haematol.2019.232124
  78. McDermid JM, Hennig BJ, van der Sande M, Hill AV, Whittle HC, Jaye A, Prentice AM. Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study. BMC Infect Dis 2013;13:48. https://doi.org/10.1186/1471-2334-13-48
  79. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13. https://doi.org/10.1016/s0140-6736(20)30211-7
  80. Edeas M, Saleh J, Peyssonnaux C. Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? Int J Infect Dis 2020;97:303-5. https://doi.org/10.1016/j.ijid.2020.05.110
  81. Dalamaga M, Karampela I, Mantzoros CS. Commentary: could iron chelators prove to be useful as an adjunct to COVID-19 treatment regimens? Metabolism 2020;108:154260. https://doi.org/10.1016/j.metabol.2020.154260
  82. Garrick M, Ghio AJ. Iron chelation may harm patients with COVID-19. Eur J Clin Pharmacol 2021;77:265-6. https://doi.org/10.1007/s00228-020-02987-w
  83. Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. Serum iron level as a potential predictor of coronavirus disease 2019 severity and mortality: a retrospective study. Open Forum Infect Dis 2020;7:ofaa250. https://doi.org/10.1093/ofid/ofaa250
  84. Rayman MP. Selenium and human health. Lancet 2012;379:1256-68. https://doi.org/10.1016/S0140-6736(11)61452-9
  85. Bellinger FP, Raman AV, Reeves MA, Berry MJ. Regulation and function of selenoproteins in human disease. Biochem J 2009;422:11-22. https://doi.org/10.1042/BJ20090219
  86. Avery JC, Hoffmann PR. Selenium, selenoproteins, and immunity. Nutrients 2018;10:1203. https://doi.org/10.3390/nu10091203
  87. Saeed F, Nadeem M, Ahmed RS, Nadeem MT, Arshad MS, Ullah A. Studying the impact of nutritional immunology underlying the modulation of immune responses by nutritional compounds-a review. Food Agric Immunol 2016;27:205-29. https://doi.org/10.1080/09540105.2015.1079600
  88. Lee YH, Lee SJ, Lee MK, Lee WY, Yong SJ, Kim SH. Serum selenium levels in patients with respiratory diseases: a prospective observational study. J Thorac Dis 2016;8:2068-78. https://doi.org/10.21037/jtd.2016.07.60
  89. Loscalzo J. Keshan disease, selenium deficiency, and the selenoproteome. N Engl J Med 2014;370:1756-60. https://doi.org/10.1056/NEJMcibr1402199
  90. Beck MA, Handy J, Levander OA. Host nutritional status: the neglected virulence factor. Trends Microbiol 2004;12:417-23. https://doi.org/10.1016/j.tim.2004.07.007
  91. Bermano G, Meplan C, Mercer DK, Hesketh JE. Selenium and viral infection: are there lessons for COVID-19? Br J Nutr 2021;125:618-27. https://doi.org/10.1017/S0007114520003128
  92. Yu L, Sun L, Nan Y, Zhu LY. Protection from H1N1 influenza virus infections in mice by supplementation with selenium: a comparison with selenium-deficient mice. Biol Trace Elem Res 2011;141:254-61. https://doi.org/10.1007/s12011-010-8726-x
  93. Broome CS, McArdle F, Kyle JA, Andrews F, Lowe NM, Hart CA, Arthur JR, Jackson MJ. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 2004;80:154-62. https://doi.org/10.1093/ajcn/80.1.154
  94. Ivory K, Prieto E, Spinks C, Armah CN, Goldson AJ, Dainty JR, Nicoletti C. Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults. Clin Nutr 2017;36:407-15. https://doi.org/10.1016/j.clnu.2015.12.003
  95. Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr 2020;111:1297-9. https://doi.org/10.1093/ajcn/nqaa095
  96. Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L. Selenium deficiency is associated with mortality risk from COVID-19. Nutrients 2020;12:2098. https://doi.org/10.3390/nu12072098
  97. Tattoli I, Carneiro LA, Jehanno M, Magalhaes JG, Shu Y, Philpott DJ, Arnoult D, Girardin SE. NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK pathways by inducing reactive oxygen species production. EMBO Rep 2008;9:293-300. https://doi.org/10.1038/sj.embor.7401161
  98. Xu J, Gong Y, Sun Y, Cai J, Liu Q, Bao J, Yang J, Zhang Z. Impact of selenium deficiency on inflammation, oxidative stress, and phagocytosis in mouse macrophages. Biol Trace Elem Res 2020;194:237-43. https://doi.org/10.1007/s12011-019-01775-7
  99. Mahmoodpoor A, Hamishehkar H, Shadvar K, Ostadi Z, Sanaie S, Saghaleini SH, Nader ND. The effect of intravenous selenium on oxidative stress in critically ill patients with acute respiratory distress syndrome. Immunol Invest 2019;48:147-59. https://doi.org/10.1080/08820139.2018.1496098
  100. Allegra A, Tonacci A, Pioggia G, Musolino C, Gangemi S. Vitamin deficiency as risk factor for SARS-CoV-2 infection: correlation with susceptibility and prognosis. Eur Rev Med Pharmacol Sci 2020;24:9721-38.