Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe
Kamil Demircan, Thilo Samson Chillon, Tommy Bracken, Ilaria Bulgarelli, Irene Campi, Gijs Du Laing, Samira Fafi-Kremer, Laura Fugazzola, Alejandro Abner Garcia, Raban Heller, David J Hughes, Louis Ide, Georg Jochen Klingenberg, Pawel Komarnicki, Zbigniew Krasinski, Alain Lescure, Patrick Mallon, Arash Moghaddam, Luca Persani, Mirko Petrovic, Marek Ruchala, Morgane Solis, Linos Vandekerckhove, Lutz Schomburg
Frontiers in Immunology, doi:10.3389/fimmu.2022.1022673
Introduction: Certain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe. Methods: Serum samples from 551 COVID-19 patients (including 87 nonsurvivors) who had participated in observational studies in Europe
Ethics statement The studies involving human participants were reviewed and approved by Local Ethics Committee of JPH Ghent and UZ Gent, Institutional review boards of the Strasbourg University Hospitals, Bavaria Ethik-Kommission der Bayerischen Landesärztekammer, Local Irish institutional review boards, ethics committee of Istituto Auxologico Italiano in Milan, Italy, Bioethical Committee at Poznan University of Medical Sciences. The patients/participants provided their written informed consent to participate in this study.
Author contributions KD: conceptualization, methodology, software, formal analysis, investigation, data curation, writing -original draft, and visualization; TC: conceptualization, methodology, software, formal analysis, investigation, data curation, writing -original draft, and visualization; TB: conceptualization, resources, and writing -review and editing; IB: conceptualization, resources, and writing -review and editing; IC: conceptualization, resources, and writing -review and editing; GDL: conceptualization, resources, and writing -review and editing; SF-K: conceptualization, resources, and writing -review and editing; LF: conceptualization, resources, and writingreview andediting;AG:conceptualization,resources,andwriting-reviewand
Conflict of interest LS holds shares of selenOmed GmbH, a company involved in selenium status assessment. The remaining authors declare that the research was conducted in the absence of any commercial or financial..
References
Adjepong, Jahangir, Malik, Kurmis, Greenwood et al., Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US preventive services task force recommendation statement, J Burn Care Res,
doi:10.1001/jama.2022.8970Andreini, Banci, Bertini, Rosato, Counting the zinc-proteins encoded in the human genome, J Proteome Res,
doi:10.1021/pr050361jBerger, Manzanares, Micronutrients early in critical illness, selective or generous, enteral or intravenous?, Curr Opin Clin Nutr Metab Care,
doi:10.1097/MCO.0000000000000724Bielsa-Berrocal, Bordeje-Laguna, Tural-Llàcher, Barallat, Manresa-Domıńguez, Low levels of few micronutrients may impact COVID-19 disease progression: An observational study on the first wave, Metabolites,
doi:10.3390/metabo11090565Cabral, Kuxhaus, Eichelmann, Kopp, Alker et al., Trace element profile and incidence of type 2 diabetes, cardiovascular disease and colorectal cancer: results from the EPIC-potsdam cohort study, Eur J Nutr,
doi:10.1007/s00394-021-02494-3Campi, Bulgarelli, Dubini, Perego, Tortorici et al., The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection, Eur J Endocrinol,
doi:10.1530/EJE-20-1391Campi, Gennari, Merlotti, Mingiano, Frosali et al., Vitamin d and COVID-19 severity and related mortality: a prospective study in Italy, BMC Infect Dis,
doi:10.1186/s12879-021-06281-7Chen, Ma, Yu, Jiang, Wang et al., Geographical distribution of trace elements (selenium, zinc, iron, copper) and case fatality rate of COVID-19: a national analysis across conterminous USA, Environ Geochemistry Health,
doi:10.1007/s10653-022-01204-0Chillon, Maares, Demircan, Hackler, Sun et al., Humoral immune response to COVID-19 mRNA vaccination in relation to selenium status, Front Immunol,
doi:10.1016/j.redox.2022.102242Daniel, Bouras, Tsilidis, Hughes, Genetically predicted circulating concentrations of micronutrients and COVID-19 susceptibility and severity: A mendelian randomization study, Front Nutr,
doi:10.3389/fnut.2022.842315Duntas, Benvenga, Selenium: an element for life, Endocrine
Forceville, Van Antwerpen, Preiser, Selenocompounds and sepsis: Redox bypass hypothesis for early diagnosis and treatment: Part a-early acute phase of sepsis: An extraordinary redox situation (Leukocyte/Endothelium interaction leading to endothelial damage), Antioxid Redox Signal,
doi:10.1089/ars.2020.8063Freeland-Graves, Sachdev, Binderberger, Sosanya, Stoffaneller et al., A review of dietary selenium intake and selenium status in Europe and the middle East, J Trace Elements Med Biol,
doi:10.3390/nu7031494Gonzalez, Riboli, Diet and cancer prevention: Contributions from the European prospective investigation into cancer and nutrition (EPIC) study, Eur J Cancer,
doi:10.1016/j.ejca.2010.07.025Gupta, Brazier, Lowe, Zinc deficiency in low-and middleincome countries: prevalence and approaches for mitigation, J Hum Nutr Diet,
doi:10.1111/jhn.12791Haase, Schomburg, You'd better zinc-trace element homeostasis in infection and inflammation, Nutrients,
doi:10.3390/nu11092078Hackler, Heller, Sun, Schwarzer, Diegmann et al., Relation of serum copper status to survival in COVID-19, Nutrients,
doi:10.3390/nu13061898Hargreaves, Mantle, Landucci, Mancinelli, Gaudio et al., Supplementation with selenium and coenzyme Q10 in critically ill patients,
doi:10.12968/hmed.2019.80.10.589Heller, Sun, Hackler, Seelig, Seibert et al., Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity, Redox Biol,
doi:10.1007/s10534-021-00355-4Hoeflich, Hollenbach, Behrends, Hoeg, Stosnach et al., Zinc status of vegetarians during pregnancy: A systematic review of observational studies and meta-analysis of zinc intake, Br J Nutr,
doi:10.3390/nu7064512Hughes, Fedirko, Jenab, Schomburg, Meplan et al., Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort, Int J Cancer
Jahromi, Tabriz, Togha, Ariyanfar, Ghorbani et al., The correlation between serum selenium, zinc, and COVID-19 severity: an observational study, BMC Infect Dis,
doi:10.1186/s12879-021-06617-3Jehan, Cartier, Bucharles, Anouar, Lihrmann et al., Emerging roles of ER-resident selenoproteins in brain physiology and physiopathology, Redox Biol,
doi:10.1016/j.redox.2022.102412Jin, Mulesa, Rouillet, Trace elements in parenteral nutrition: Considerations for the prescribing clinician, Nutrients,
doi:10.3390/nu9050440Jones, Droz, Greve, Gottschalk, Poffet et al., Evidence-based recommendations for an optimal prenatal supplement for women in the U.S., part two: Minerals, Matern Health Neonatol Perinatol,
doi:10.3390/nu13061849Kaeuffer, Hyaric, Fabacher, Mootien, Dervieux et al., Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in north-Eastern France, Eurosurveillance,
doi:10.2807/1560-7917.ES.2020.25.48.2000895Kenny, Mccann, 'brien, Savinelli, Tinago et al., Identification of distinct long COVID clinical phenotypes through cluster analysis of self-reported symptoms, Open Forum Infect Dis,
doi:10.1093/ofid/ofac060Kenny, Negi, Reilly, Garcia-Leon, Alalwan et al., Performance and validation of an adaptable multiplex assay for detection of serologic response to SARS-CoV-2 infection or vaccination, medRxiv,
doi:10.1101/2022.05.16.22275163Kocyigit, Erel, Gurel, Avci, Aktepe, Alterations of serum selenium, zinc, copper, and iron concentrations and some related antioxidant enzyme activities in patients with cutaneous leishmaniasis, Biol Trace Element Res,
doi:10.1007/BF02789102Laing, Petrovic, Lachat, Boevre, Klingenberg et al., Course and survival of COVID-19 patients with comorbidities in relation to the trace element status at hospital admission, Nutrients,
doi:10.3390/nu13103304Li, Jiang, Li, Li, Zhou et al., Glutathione peroxidase 4-regulated neutrophil ferroptosis induces systemic autoimmunity, Nat Immunol,
doi:10.1038/s41590-021-00993-3Marino, Marino, Valla, Beattie, Verbruggen et al., Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence, Clin Nutr,
doi:10.3390/nu14020283Moghaddam, Heller, Sun, Seelig, Cherkezov et al., Selenium deficiency is associated with mortality risk from COVID-19, Nutrients,
doi:10.3390/nu12072098Negro, Greco, Mangieri, Pezzarossa, Dazzi et al., The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies, J Clin Endocrinol Metab
Nichol, Herdman, Sattar, Dwyer, St et al., Changes in the concentrations of plasma selenium and selenoproteins after minor elective surgery: further evidence for a negative acute phase response?, Biol Trace Element Res,
doi:10.1007/s12011-011-9107-9Obbagy, English, Psota, Wong, Butte et al., Complementary feeding and micronutrient status: a systematic review, Am J Clin Nutr,
doi:10.1093/ajcn/nqy266Oh, Keats, Bhutta, Vitamin and mineral supplementation during pregnancy on maternal, birth, child health and development outcomes in low-and middle-income countries: A systematic review and meta-analysis, Nutrients,
doi:10.3390/nu12020491Pitts, Hoffmann, Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis, Cell Calcium,
doi:10.1016/j.ceca.2017.05.001Pour, Yahyavi, Karimi, Khamaneh, Milani et al., Serum trace elements levels and clinical outcomes among Iranian COVID-19 patients, Int J Infect Dis,
doi:10.3390/nu14071407Prasad, Maares, Haase, A guide to human zinc absorption: General overview and recent advances of in vitro intestinal models, Nutrients,
doi:10.3390/nu12030762Rayman, Taylor, Zhang, The relevance of selenium to viral disease with special reference to SARS-CoV-2 and COVID-19, Proc Nutr Soc,
doi:10.1017/S0029665122002646Riboli, Hunt, Slimani, Ferrari, Norat et al., European Prospective investigation into cancer and nutrition (EPIC): study populations and data collection, Public Health Nutr,
doi:10.1079/PHN2002394Ringneŕ, What is principal component analysis?, Nat Biotechnol
Scarpellini, Balsiger, Maurizi, Rinninella, Gasbarrini et al., Zinc and gut microbiota in health and gastrointestinal disease under the COVID-19 suggestion, Immun Ageing,
doi:10.1186/1742-4933-6-9Schomburg, Schweizer, Köhrle, Selenium and selenoproteins in mammals: extraordinary, essential, enigmatic, Cell Mol Life Sci CMLS,
doi:10.1007/s00018-004-4114-zSchomburg, Selenium deficiency due to diet, pregnancy, severe illness, or COVID-19-A preventable trigger for autoimmune disease, Int J Mol Sci,
doi:10.3390/ijms22168532Seyrek, Kocyigit, Erel, Essential trace elements selenium, zinc, copper, and iron concentrations and their related acute-phase proteins in patients with vivax malaria, Biol Trace Elem Res,
doi:10.1385/BTER:106:2:107Singh, Diwaker, Singh, Singh, Immunity et al., Assessment of the role of zinc in the prevention of COVID-19 infections and mortality: A retrospective study in the Asian and European population, Front Immunol,
doi:10.3390/nu13062113Skalny, Timashev, Aschner, Aaseth, Chernova et al., Serum zinc, copper, and other biometals are associated with COVID-19 severity markers, Metabolites,
doi:10.3390/metabo11040244Sobczyk, Gaunt, The effect of circulating zinc, selenium, copper and vitamin K1 on COVID-19 outcomes: A mendelian randomization study, Nutrients,
doi:10.3390/nu14020233Turnlund, Jacob, Keen, Strain, Kelley et al., Longterm high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men, Am J Clin Nutr,
doi:10.1093/ajcn/79.6.1037Voelkle, Gregoriano, Neyer, Koch, Kutz et al., Prevalence of micronutrient deficiencies in patients hospitalized with COVID-19: An observational cohort study, Nutrients,
doi:10.3390/nu14091862Xia, Wang, Dai, Zhang, Zhou et al., Selenoprotein K is essential for the migration and phagocytosis of immature dendritic cells, Antioxidants,
doi:10.3390/antiox11071264Xu, Hao, Li, Li, Wang et al., Distribution of selenium and zinc in soil-crop system and their relationship with environmental factors, Chemosphere,
doi:10.1016/j.chemosphere.2019.125289Zhang, Li, Du, Sang, Liu et al., Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level, J Transl Med,
doi:10.1186/s12967-022-03566-6Zhang, Taylor, Bennett, Saad, Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, Am J Clin Nutr,
doi:10.1093/ajcn/nqaa095Zhang, Zhang, Lu, Zhang, Zhang et al., Association between fatality rate of COVID-19 and selenium deficiency in China, BMC Infect Dis,
doi:10.1186/s12879-021-06167-8Ziaei, Rahman, Raqib, Lonnerdal, Ekstrom, A prenatal multiple micronutrient supplement produces higher maternal vitamin b-12 concentrations and similar folate, ferritin, and zinc concentrations as the standard 60-mg iron plus 400-mug folic acid supplement in rural Bangladeshi women, J Nutr,
doi:10.3945/jn.116.235994
