Overview of the Potential Role of Trace Elements in COVID-19
doi.org/10.26538/tjnpr/v6i6.2
Keywords:
Copper, COVID-19, Iron, Selenium, Vitamins, ZincAbstract
COVID-19 is constantly evolving due to genetic mutation, and different strains have been discovered all over the world. These variants appear to be transmitted more strongly than other types, potentially contributing to an increase in cases and deaths. Currently, there are several COVID-19 vaccines on the market. Despite the availability of these commercial vaccines, the number of admitted patients continues to rise in various parts of the world. The vaccines' consistency and efficacy, in terms of variations between effects of different brands, remain ambiguous due to viral variants. Trace element deficiencies have been shown to reduce the immune response to invader pathogens and contribute to global health issues. Deficiencies in vitamins, copper, selenium, and zinc have been shown in clinical trials to alter the immune response and increase the risk of viral infections. Due to the antiviral and anti-inflammatory properties of these micronutrients, dietary supplementation of these components is likely to increase the immune response and lower the severity of COVID-19 infection. Based on existing research, therapeutic use of important trace element supplements, such as minerals (Cu, Se, and Zn) or vitamins (such as vitamins D and C), may be a preventive and consistent strategy for strengthening the immune system against the emerging pandemic COVID-19 and its novel variants.
References
Ciotti M, Ciccozzi M, Terrinoni A, Jiang WC, Wang CB, Bernardini S. The COVID-19 pandemic. Crit Rev Clin Lab Sci. 2020; 57(6):365-388.
Hanff TC, Mohareb AM, Giri J, Cohen JB, Chirinos JA. Thrombosis in COVID‐19. Am J Hematol. 2020; 95(12):1578-1589.
Dhok A, Butola LK, Anjankar A, Shinde AD, Kute PK, Jha RK. Role of Vitamins and Minerals in Improving Immunity during Covid-19 Pandemic-A Review. J Evol Med Dent Sci. 2020; 9(32):2296-301.
Merkhan MM, Abdulrazzaq GM, Al-Taii HA. Coronavirus (COVID-19): preventive measures and potential interventions. Eur J Mol Clin Med. 2021; 7(10):1388-1399.
Darweesh O, Abdulrazzaq GM, Al-Zidan RN, Bebane P, Merkhan M, Aldabbagh R, AlOmari N. Evaluation of the Pharmacologic Treatment of COVID-19 Pandemic in Iraq. Curr Pharmacol Rep. 2021; 7(4):171-178.
Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020; 11:1446.
Mukherjee K. COVID-19 and cytokine storm. Inter J Bioinf Biol Sci. 2020; 8(1):18-26.
Ebadi M, Montano-Loza AJ. Perspective: improving vitamin D status in the management of COVID-19. Eur J Clin Nutr. 2020; 74(6):856-859.
Razdan K, Singh K, Singh D. Vitamin D levels and COVID-19 susceptibility: is there any correlation? Medicine in drug discovery. 2020; 7:100051.
Molloy EJ and Murphy N. Vitamin D, Covid-19, and children. Ir Med J. 2020; 113(4):64.
Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008; 88(2):491S-499S.
Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int. 2010; 78(2):140-145.
Kumar R, Rathi H, Haq A, Wimalawansa SJ, Sharma A. Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus Res. 2021; 292:198235.
Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, Schou M, Phelps M, Gislason GH, Gerds TA, Torp-Pedersen C. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. J Am Med Assoc. 2020; 324(2):168-177.
Bilezikian JP, Bikle D, Hewison M, Lazaretti-Castro M, Formenti AM, Gupta A, Madhavan MV, Nair N, Babalyan V, Hutchings N, Napoli N. Mechanisms in endocrinology: vitamin D and COVID-19. Eur J Endocrinol. 2020; 183(5):R133-147.
Fedele D, De Francesco A, Riso S, Collo A. Obesity, malnutrition, and trace element deficiency in the coronavirus disease (COVID-19) pandemic: an overview. Nutr. 2021; 81:1-14.
Althanoon ZA and Merkhan MM. Effects of zinc supplementation on metabolic status in patients with metabolic syndrome. Acta Pol Pharm. 2021; 78(4):521-526.
Calder PC. Nutrition, immunity, and COVID-19. BMJ Nutr Prev Health. 2020; 3(1):74.
Pal A, Squitti R, Picozza M, Pawar A, Rongioletti M, Dutta AK, Sahoo S, Goswami K, Sharma P, Prasad R. Zinc and COVID-19: basis of current clinical trials. Biol Trace Elem Res. 2021; 199(8):2882-2892.
Gromova OA and Torshin IY. The importance of zinc in maintaining the activity of antiviral innate immunity proteins: analysis of publications on COVID-19. J Prev Med Pub Health. 2020; 3(23):131-139.
Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, Black RE. Zinc for severe pneumonia in very young children: a double-blind placebo-controlled trial. The Lancet. 2004; 363(9422):1683-1688.
Ebrahimzadeh-Attari V, Panahi G, Hebert JR, Ostadrahimi A, Saghafi-Asl M, Lotfi-Yaghin N, Baradaran B. Nutritional approach for increasing public health during the pandemic of COVID-19: A comprehensive review of antiviral nutrients and nutraceuticals. Health Promot Perspect. 2021; 11(2):119.
Stratton CW, Tang YW, Lu H. Pathogenesis‐directed therapy of 2019 novel coronavirus disease. J Med Virol. 2021; 93(3):1320-1342.
Nedjimi B. Can trace element supplementations (Cu, Se, and Zn) enhance human immunity against COVID-19 and its new variants?. Beni-Seuf Univ J Appl. 2021; 10(1):1-5.
Hemilä H, Haukka J, Alho M, Vahtera J, Kivimäki M. Zinc acetate lozenges for the treatment of the common cold: a randomized controlled trial. Br Med J Open. 2020; 10(1):e031662.
Jia W, Song Y, Yang L, Kong J, Boczek T, He Z, Wang Y, Zhang X, Hu H, Shao D, Tang H. The changes of serum zinc, copper, and selenium levels in epileptic patients: A systematic review and meta-analysis. Exp Rev Clin Pharmacol. 2020; 13(9):1047-1058.
Vogel-González M, Talló-Parra M, Herrera-Fernández V, Pérez-Vilaró G, Chillón M, Nogués X, Gómez-Zorrilla S, López-Montesinos I, Arnau-Barrés I, Sorli-Redó ML, Horcajada JP. Low zinc levels at admission associates with poor clinical outcomes in SARS-CoV-2 infection. Nutr.
; 13(2):562.
Kaye K, Paprottka F, Escudero R, Casabona G, Montes J, Fakin R, Moke L, Stasch T, Richter D, Benito-Ruiz J. Elective, non-urgent procedures, and aesthetic surgery in the wake of SARS–COVID-19: considerations regarding safety, feasibility, and impact on clinical management.
Aesthetic Plast Surg. 2020; 44(3):1014-1042.
Kieliszek M. Selenium–fascinating microelement, properties, and sources in food. Mol. 2019; 24(7):1298.
Beck MA, Nelson HK, Shi Q, Van Dael P, Schiffrin EJ, Blum S, Barclay D, Levander OA. Selenium deficiency increases the pathology of an influenza virus infection. The FASEB J. 2001; 15(8):1481-1483.
Narota A, Puri G, Singh VP, Kumar A, Naura AS. COVID-19, and ARDS: Update on Preventive and Therapeutic Venues. Curr Mol Med. 2021; 22(4):312-324.
Percival SS. Copper and immunity. Am J Clin Nutr. 1998; 67(5):1064S-1068S.
Fooladi S, Matin S, Mahmoodpoor A. Copper as a potential adjunct therapy for critically ill COVID-19 patients. Clin Nutr ESPEN. 2020; 40:90-91.
Bussière FI, Mazur A, Fauquert JL, Labbe A, Rayssiguier Y, Tridon A. High magnesium concentration in vitro decreases human leukocyte activation. Magnesium Res. 2002; 15(1-2):43-48.
Laires MJ and Monteiro C. Exercise, magnesium, and immune function. Magnes Res. 2008; 21(2):92-96.
Landon RA and Young EA. Role of magnesium in the regulation of lung function. J Am Diet Assoc. 1993; 93(6):674-677.
Janssen R. Magnesium to counteract elastin degradation and vascular calcification in chronic obstructive pulmonary disease. Med Hyp. 2017; 107(2):74-77.
Son EW, Lee SR, Choi HS, Koo HJ, Huh JE, Kim MH, Pyo S. Effects of supplementation with higher levels of manganese and magnesium on immune function. Arch Pharm Res. 2007; 30(6):743-749.
Girelli D, Marchi G, Busti F, Vianello A. Iron metabolism in infections: Focus on COVID-19. Semin hematol. 2021; 58(3):182-187.
Perricone C, Bartoloni E, Bursi R, Cafaro G, Guidelli GM, Shoenfeld Y, Gerli R. COVID-19 as part of the hyperferritinemia syndromes: the role of iron depletion therapy. Immunol Res. 2020; 68(4):213–224.
Yu L, Peel GK, Cheema FH, Lawrence WS, Bukreyeva N, Jinks CW, Peel JE, Peterson JW, Paessler S, Hourani M, Ren Z. Catching and killing of airborne SARS-CoV-2 to control spread of COVID-19 by a heated air disinfection system. Mat today Phy. 2020; 15(1):1-5.
Salnikow K, Su W, Blagosklonny MV, Costa M. Carcinogenic metals induce hypoxia-inducible factorstimulated transcription by reactive oxygen speciesindependent mechanism. Cancer Res. 2000; 60(13):3375-3378.
Rajkumar RP. Lithium as a candidate treatment for COVID‐19: promises and pitfalls. Drug Dev Res. 2020; 81(7):782-785.
Spuch C, López-García M, Rivera-Baltanás T, RodríguesAmorím D, Olivares JM. Does lithium deserve a place in the treatment against COVID-19? A preliminary observational study in six patients, case report. Front Pharm. 2020; 11(2):1-8.
Viel T, Chinta S, Rane A, Chamoli M, Buck H, Andersen J. Microdose lithium reduces cellular senescence in human astrocytes-a potential pharmacotherapy for COVID-19?.Aging. 2020; 12(11):10035-10040.
Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front Immunol. 2019; 9(2):1-19.
Matsui T, Takahashi R, Nakao Y, Koizumi T, Katakami Y, Mihara K, Sugiyama T, Fujita T. 1, 25-dihydroxy vitamin D3-regulated expression of genes involved in human Tlymphocyte proliferation and differentiation. Cancer Res. 1986; 46(11):5827-5831.
Reichel H, Koeffler HP, Tobler A, Norman AW. 1 alpha, 25-dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Nat Acad Sci. 1987; 84(10):3385-3389.
Rigby WF, Denome S, Fanger MW. Regulation of lymphokine production and human T lymphocyte activation by 1, 25-dihydroxy vitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest. 1987; 79(6):1659-1664.
Zosky GR, Berry LJ, Elliot JG, James AL, Gorman S, Hart PH. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Res Crit Care Med. 2011; 183(10):1336-1343.
Beyhan-Sagmen S, Baykan O, Balcan B, Ceyhan B. Association between severe vitamin D deficiency, lung function and asthma control. Arch Bronch. 2017; 53(4):186-191.
Maggini S, Beveridge S, Sorbara PJ, Senatore G. Feeding the immune system: the role of micronutrients in restoring resistance to infections. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nut Nat Res. 2008; 3(098):1-21.
Carr NB and Melcher CP, editors. Wyoming Basin rapid ecoregional assessment. US Department of the Interior, US Geological Survey; 2017; 17(1):233-238.
Prentice S. They are what you eat: can nutritional factors during gestation and early infancy modulate the neonatal immune response? Front Immunol. 2017; 8(4):1-20.
Kim H, Jang M, Kim Y, Choi J, Jeon J, Kim J, Hwang YI, Kang JS, Lee WJ. Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection. J Pharm Pharmacol. 2016; 68(3):406-420.
McGill JL, Kelly SM, Guerra-Maupome M, Winkley E, Henningson J, Narasimhan B, Sacco RE. Vitamin A deficiency impairs the immune response to intranasal vaccination and RSV infection in neonatal calves. Sci Rep. 2019; 9(1):1-4.
Wishart K. Increased micronutrient requirements during physiologically demanding situations: a review of the current evidence. Vitam Miner. 2017; 6(166):1318-2376.
Pettifor JM, Zlotkin S, editors. Micronutrient deficiencies during the weaning period and the first years of life. Karger Medical and Scientific Publishers. 2004; 27(1):200-204.
Center MI. L.P. Institute (Ed.), Immunity In Brief, 2017; 22(1):218-222.
Haryanto B, Suksmasari T, Wintergerst E, Maggini SJ. Multivitamin supplementation supports immune function and ameliorates conditions triggered by reduced air quality. Vitam Miner. 2015; 4(3):1-5.
Traber MG and Atkinson J. Vitamin E, antioxidant and nothing more. Free Rad Bio Med. 2007; 43(1):4-15.
Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Inf Dis. 2017; 17(1):1-10.
Li YQ, Li ZL, Zhao WJ, Wen RX, Meng QW, Zeng Y. Synthesis of stilbene derivatives with inhibition of SARS coronavirus replication. Eur J Med Chem. 2006; 41(9):1084-1089.
Jo S, Kim H, Kim S, Shin DH, Kim MS. Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors. Chem Bio Drug Des. 2019; 94(6):2023-2030.
Park HR, Yoon H, Kim MK, Lee SD, Chong Y. Synthesis and antiviral evaluation of 7-O-aryl methyl quercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV). Arch Pharm Res. 2012; 35(1):77-85.
Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017; 17:136-144.
Bhatia S, Giri S, Lal AF, Singh S. Identification of potential inhibitors of dietary polyphenols for SARS-CoV-2 M protease: An in silico study. One Health Bull. 2020; 1:21-9.
Nguyen TT, Woo HJ, Kang HK, Nguyen VD, Kim YM, Kim DW, Ahn SA, Xia Y, Kim D. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotech Lett. 2012; 34(5):831-838.
Pár A, Rőth E, Miseta A, Hegedüs G, Pár G, Hunyady B, Vincze Á. Effects of silymarin supplementation in chronic hepatitis C patients treated with peg-interferon+ ribavirin. A placebo-controlled double-blind study. OrvosiHetilap. 2009; 150(2):73-79.
Vázquez-Calvo Á, Jiménez de Oya N, Martín-Acebes MA, Garcia-Moruno E, Saiz JC. Antiviral properties of the natural polyphenols delphinidin and epigallocatechingallate against the flaviviruses West Nile virus, Zika virus, and dengue virus. Front Microbiol. 2017; 8(3):1-8.
Sokmen M, Angelova M, Krumova E, Pashova S, Ivancheva S, Sokmen A, Serkedjieva J. In vitro antioxidant activity of polyphenol extracts with antiviral properties from Geranium sanguineum L. Life Sci. 2005; 76(25):2981-2993.
Iyer M, Jayaramayya K, Subramaniam MD, Lee SB, Dayem AA, Cho SG, Vellingiri B. COVID-19: an update on diagnostic and therapeutic approaches. BMB Rep. 2020; 53(4):191.
Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutr. 2020; 12(1):1-28.
Sun J and De Vos P. Immunomodulatory functions of nutritional ingredients in health and disease. Front Immunol. 2019; 10:1-3.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020; 38(1):1-9.
Saeed F, Nadeem M, Ahmed RS, Tahir Nadeem M, 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(2):205-229.
Alpert PT. The role of vitamins and minerals on the immune system. Health Care Manag Prac. 2017; 29(3):199-202.
Zoroddu MA, Aaseth J, Crisponi G, Medici S, Peana M, Nurchi VM. The essential metals for humans: a brief overview. J Inorg Biochem. 2019; 195(6):120-129.
Chew BP and Park JS. Carotenoid action on the immune response. J Nut. 2004; 134(1):257S-61S.
Yin Z, Pintea V, Lin Y, Hammock BD, Watsky MA. Vitamin D enhances corneal epithelial barrier function. Invest Ophthvis Sci. 2011; 52(10):7359-7364.
Hemilä H. Vitamin C and infections. Nutr. 2017; 9(4):1-28.
Lin PH, Sermersheim M, Li H, Lee PH, Steinberg SM, Ma J. Zinc in wound healing modulation. Nutr. 2017; 10(1):1-16.
Biesalski HK. Nutrition meets the microbiome: micronutrients and the microbiota. Annthe New York Acad Sci. 2016; 1372(1):53-64.
Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of dietary and microbial vitamin B family in the regulation of host immunity. Front Nutr. 2019; 6(6):48-56.
Zhou JH, Wang YN, Chang QY, Ma P, Hu Y, Cao X. Type III interferons in viral infection and antiviral immunity. Cell Physiol Biochem. 2018; 51(1):173-185.
Lee SH, Kim SY, Jung K, Cho ML. Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis. Sci Rep. 2017; 7(1):1-9.
McCarty MF and Di Nicolantonio JJ. Nutraceuticals have the potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Card Dis. 2020; 63(3):383.
Pae M, Meydani SN, Wu D. The role of nutrition in enhancing immunity in aging. Aging Dis. 2012; 3(1):91-129.
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