Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework

Galmés et al., Nutrients, doi:10.3390/nu12092738

Sep 2020

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Ecological study of European countries analyzing 10 vitamins and minerals endorsed by the European Food Safety Authority as having sufficient evidence for a causal relationship between intake and optimal immune system function: vitamins D, A, C, B6, B9, B12, zinc, copper, iron, and selenium.

Intake levels of all 10 showed an inverse correlation with the relative mortality rate, while all except vitamin B6 and selenium showed an inverse correlation with incidence and mortality. Most individual correlations did not reach statistical significance. Authors note greater association in populations genetically predisposed towards lower micronutrient status.

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This study includes diet, selenium, zinc, vitamin C, vitamin A, and vitamin D.

Galmés et al., 8 Sep 2020, retrospective, peer-reviewed, 3 authors.

Contact: francisca.serra@uib.es (corresponding author), s.galmes@uib.cat, andreu.palou@uib.es.

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Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework

Sebastià Galmés, Francisca Serra, Andreu Palou

Nutrients, doi:10.3390/nu12092738

The pandemic caused by the new coronavirus has caused shock waves in many countries, producing a global health crisis worldwide. Lack of knowledge of the biological mechanisms of viruses, plus the absence of effective treatments against the disease (COVID-19) and/or vaccines have pulled factors that can compromise the proper functioning of the immune system to fight against infectious diseases into the spotlight. The optimal status of specific nutrients is considered crucial to keeping immune components within their normal activity, helping to avoid and overcome infections. Specifically, the European Food Safety Authority (EFSA) evaluated and deems six vitamins (D, A, C, Folate, B 6 , B 12 ) and four minerals (zinc, iron, copper and selenium) to be essential for the normal functioning of the immune system, due to the scientific evidence collected so far. In this report, an update on the evidence of the contribution of nutritional factors as immune-enhancing aspects, factors that could reduce their bioavailability, and the role of the optimal status of these nutrients within the COVID-19 pandemic context was carried out. First, a non-systematic review of the current state of knowledge regarding the impact of an optimal nutritional status of these nutrients on the proper functioning of the immune system as well as their potential role in COVID-19 prevention/treatment was carried out by searching for available scientific evidence in PubMed and LitCovid databases. Second, a compilation from published sources and an analysis of nutritional data from 10 European countries was performed, and the relationship between country nutritional status and epidemiological COVID-19 data (available in the Worldometers database) was evaluated following an ecological study design. Furthermore, the potential effect of genetics was considered through the selection of genetic variants previously identified in Genome-Wide Association studies (GWAs) as influencing the nutritional status of these 10 considered nutrients. Therefore, access to genetic information in accessible databases (1000genomes, by Ensembl) of individuals from European populations enabled an approximation that countries might present a greater risk of suboptimal status of the nutrients studied. Results from the review approach show the importance of maintaining a correct nutritional status of these 10 nutrients analyzed for the health of the immune system, highlighting the importance of Vitamin D and iron in the context of COVID-19. Besides, the ecological study demonstrates that intake levels of relevant micronutrients-especially Vitamins D, C, B 12 , and iron-are inversely associated with higher COVID-19 incidence and/or mortality, particularly in populations genetically predisposed to show lower micronutrient status. In conclusion, nutrigenetic data provided by joint assessment of 10 essential nutrients for the functioning of the immune system and of the genetic factors that can limit their..

Supplementary Materials: The following are available online at http://www.mdpi.com/2072-6643/12/9/2738/s1, Supplementary Figure S1 . Country genotype frequencies of Single Nucleotide Polymorphisms (SNPs) involved in specific Vitamins and Minerals nutritional status. Author Contributions: Conceptualization, methodology, data curation, and writing-original draft preparationwere done by S.G., F.S., and A.P.; writing-review and editing-and supervision was performed by F.S. and A.P.; project administration and funding acquisition were carried out by A.P. All authors have read and agreed to the published version of the manuscript.

References

Abobaker, Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?, Eur. J. Clin. Pharmacol, doi:10.1007/s00228-020-02942-9

Agoro, Taleb, Quesniaux, Mura, Cell iron status influences macrophage polarization, PLoS ONE, doi:10.1371/journal.pone.0196921

Alipio, Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus, SSRN Electron. J, doi:10.2139/ssrn.3571484

Allayee, Roth, Hodis, Polyunsaturated fatty acids and cardiovascular disease: Implications for nutrigenetics, J. Nutr, doi:10.1159/000235562

Alvarez, Quon, Mullen, Casey, Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart, BMC Cardiovasc. Disord, doi:10.1186/1471-2261-13-2

Amrein, Scherkl, Hoffmann, Neuwersch-Sommeregger, Köstenberger et al., deficiency 2.0: An update on the current status worldwide, Eur. J. Clin. Nutr, doi:10.1038/s41430-020-0558-y

Andreou, Trantza, Filippou, Sipsas, Tsiodras, COVID-19: The potential role of copper and N-acetylcysteine (NAC) in a combination of candidate antiviral treatments against SARS-CoV-2, Vivo, doi:10.21873/invivo.11946

Arnaud, Kelley, Helias, Cartron, Ballif, SMIM1 is a type II transmembrane phosphoprotein and displays the Vel blood group antigen at its carboxyl-terminus, FEBS Lett, doi:10.1016/j.febslet.2015.09.029

Astle, Elding, Jiang, Allen, Ruklisa et al., The allelic landscape of human blood cell trait variation and links to common complex disease, Cell, doi:10.1016/j.cell.2016.10.042

Atherton, Kratzing, Fisher, The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus, Arch. Virol, doi:10.1007/BF01317848

Auton, Abecasis, Altshuler, Durbin, A global reference for human genetic variation, Nature, doi:10.1038/nature15393

Axelrod, Role of the B vitamins in the immune response

Baum, Wong, Ng, Tomlinson, Rainer et al., Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke, Clin. Chem. Lab. Med, doi:10.1515/CCLM.2004.256

Beck, Levander, Handy, Selenium deficiency and viral infection, J. Nutr, doi:10.1093/jn/133.5.1463S

Benyamin, Esko, Ried, Radhakrishnan, Vermeulen et al., Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis, Nat. Commun, doi:10.1038/ncomms5926

Berry, Vimaleswaran, Whittaker, Hingorani, Hyppönen, Evaluation of genetic markers as instruments for Mendelian randomization studies on vitamin D, PLoS ONE, doi:10.1371/journal.pone.0037465

Bertoldi, Gianesello, Calò, Rho kinase inhibition and the potential role of vitamin D against COVID-19, Aliment. Pharmacol. Ther, doi:10.1111/apt.15895

Besold, Culbertson, Culotta, The Yin and Yang of copper during infection, JBIC J. Biol. Inorg. Chem, doi:10.1007/s00775-016-1335-1

Biancatelli, Berrill, Catravas, Marik, Quercetin, vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19), Front. Immunol, doi:10.3389/fimmu.2020.01451

Bolondi, Russo, Gamberini, Circelli, Meca et al., Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: An observational cohort study, World J. Emerg. Surg, doi:10.1186/s13017-020-00323-2

Bonet, Ribot, Galmés, Serra, Palou, Carotenoids and carotenoid conversion products in adipose tissue biology and obesity: Pre-clinical and human studies, Biochim. Biophys. Acta Mol. Cell Biol. Lipids, doi:10.1016/j.bbalip.2020.158676

Boretti, Banik, Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome, PharmaNutrition, doi:10.1016/j.phanu.2020.100190

Brigham, Mccormack, Takemoto, Matsui, Iron Status is associated with asthma and lung function in US women, PLoS ONE, doi:10.1371/journal.pone.0117545

Brown, The metabolism of pantothenic acid, J. Biol. Chem

Buniello, Macarthur, Cerezo, Harris, Hayhurst et al., The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019, Nucleic Acids Res, doi:10.1093/nar/gky1120

Báez-Santos, St, John, Mesecar, The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds, Antiviral Res, doi:10.1016/j.antiviral.2014.12.015

Carr, A new clinical trial to test high-dose vitamin C in patients with COVID-19, Crit. Care

Carr, Vitamin C administration in the critically ill: A summary of recent meta-analyses, Crit. Care, doi:10.1186/s13054-019-2538-y

Chen, Wang, Wang, Yang, Wang et al., Pharmacological development of the potential adjuvant therapeutic agents against coronavirus disease, J. Chin. Med. Assoc, doi:10.1097/JCMA.0000000000000375

Chew, Role of carotenoids in the immune response, J. Dairy Sci, doi:10.3168/jds.S0022-0302(93)77619-5

Cifre, Díaz-Rúa, Varela-Calviño, Reynés, Pericás-Beltrán et al., Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI, Mol. Nutr. Food Res, doi:10.1002/mnfr.201600353

Cornelis, Fornage, Foy, Xun, Gladyshev et al., Genome-wide association study of selenium concentrations, Hum. Mol. Genet, doi:10.1093/hmg/ddu546

D'adamo, ; D'urso, Ryan, Yerges-Armstrong, Semba et al., A common variant in the SETD7 gene predicts serum lycopene concentrations, Nutrients, doi:10.3390/nu8020082

D'adamo, Dawson, Ryan, Yerges-Armstrong, Semba et al., The CAPN2/CAPN8 locus on chromosome 1q is associated with variation in serum alpha-carotene concentrations, J. Nutr. Nutr, doi:10.1159/000452890

D'amico, Peyrin-Biroulet, Danese, Oral iron for IBD patients: Lessons learned at time of COVID-19 pandemic, J. Clin. Med, doi:10.3390/jcm9051536

Daneshkhah, Eshein, Subramanian, Roy, Backman, The role of vitamin D in suppressing cytokine storm in COVID-19 patients and associated mortality, medRxiv, doi:10.1101/2020.04.08.20058578

De Almeida Brasiel, The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis, Clin. Nutr. ESPEN, doi:10.1016/j.clnesp.2020.06.003

Derwand, Scholz, Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today's battle against COVID-19?, Med. Hypotheses, doi:10.1016/j.mehy.2020.109815

Dhar, Mohanty, Gut microbiota and Covid-19-possible link and implications, Virus Res, doi:10.1016/j.virusres.2020.198018

Doboszewska, Wlaź, Nowak, Młyniec, Targeting zinc metalloenzymes in COVID-19, Br. J. Pharmacol, doi:10.1111/bph.15199

Ducker, Rabinowitz, One-Carbon metabolism in health and disease, Cell Metab, doi:10.1016/j.cmet.2016.08.009

Efsa, Dietary Reference Values for vitamin B6, EFSA J, doi:10.2903/j.efsa.2016.4485

Ehret, Munroe, Rice, Bochud, Johnson et al., Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk, Nature, doi:10.1038/nature10405

Elmadfa, Meyer, Nowak, Nations, Food et al., European nutrition and health report 2009, Ann. Nutr. Metab, doi:10.1159/000244607

Evans, Zhu, Dy, Heath, Madden et al., Genome-wide association study identifies loci affecting blood copper, selenium and zinc, Hum. Mol. Genet, doi:10.1093/hmg/ddt239

Farhat, Lees, Macdonald-Clarke, Amirabdollahian, Inadequacies of micronutrient intake in normal weight and overweight young adults aged 18-25 years: A cross-sectional study, Public Health, doi:10.1016/j.puhe.2018.10.016

Ferrucci, Perry, Matteini, Perola, Tanaka et al., Common variation in the β-carotene 15,15 -monooxygenase 1 gene affects circulating levels of carotenoids: A genome-wide association study, Am. J. Hum. Genet, doi:10.1016/j.ajhg.2008.12.019

Finzi, Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.06.006

Fogarty, Townsend, Ni Cheallaigh, Bergin, Martin-Loeches et al., COVID19 coagulopathy in Caucasian patients, Br. J. Haematol, doi:10.1111/bjh.16749

Fowler, Truwit, Hite, Morris, Dewilde et al., Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure, JAMA, doi:10.1001/jama.2019.11825

Galmés, Cifre, Palou, Oliver, Serra, A genetic score of predisposition to low-grade inflammation associated with obesity may contribute to discern population at risk for metabolic syndrome, Nutrients, doi:10.3390/nu11020298

Galmés, Serra, Palou, Vitamin E metabolic effects and genetic variants: A challenge for precision nutrition in obesity and associated disturbances, Nutrients, doi:10.3390/nu10121919

García, Micronutrients, immunology and inflammation: Effect of vitamin A deficiency on the immune response in obesity, Proc. Nutr. Soc, doi:10.1017/S0029665112000079

Gombart, Pierre, Maggini, A Review of micronutrients and the immune system-Working in harmony to reduce the risk of infection, Nutrients, doi:10.3390/nu12010236

Gong, Hsu, Harrison, King, Stürup et al., Genome-Wide Association Study of Serum Selenium Concentrations, Nutrients

Goodman, Huang, Shiratori, Mechanism of the biosynthesis of vitamin A from beta-carotene, J. Biol. Chem

Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin d supplementation could reduce risk of influenza and covid-19 infections and deaths, Nutrients, doi:10.3390/nu12040988

Hadizadeh, Supplementation with vitamin D in the COVID-19 pandemic?, Nutr. Rev, doi:10.1093/nutrit/nuaa081

Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab. Syndr. Clin. Res. Rev, doi:10.1016/j.dsx.2020.04.050

Hemilä, Vitamin C and infections, Nutrients, doi:10.3390/nu9040339

Hemilä, Vitamin C intake and susceptibility to pneumonia, Pediatr. Infect. Dis. J, doi:10.1097/00006454-199709000-00003

Hiedra, Lo, Elbashabsheh, Gul, Wright et al., The use of IV vitamin C for patients with COVID-19: A single center observational study, Expert Rev. Anti. Infect. Ther, doi:10.1080/14787210.2020.1794819

Hilgenfeld, From SARS to MERS: Crystallographic studies on coronaviral proteases enable antiviral drug design, FEBS J, doi:10.1111/febs.12936

Hiraoka, Kagawa, Genetic polymorphisms and folate status, Congenit. Anom, doi:10.1111/cga.12232

Hong, Hatchell, Bradfield, Bjonnes, Chesi et al., Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations, J. Clin. Endocrinol. Metab, doi:10.1210/jc.2017-01802

Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, doi:10.1016/S0140-6736(20)30183-5

Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin. Exp. Res, doi:10.1007/s40520-020-01570-8

Jayawardena, Sooriyaarachchi, Chourdakis, Jeewandara, Ranasinghe, Enhancing immunity in viral infections, with special emphasis on COVID-19: A review, Diabetes Metab. Syndr. Clin. Res. Rev, doi:10.1016/j.dsx.2020.04.015

Jiang, O'reilly, Aschard, Hsu, Richards et al., Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels, Nat. Commun, doi:10.1038/s41467-017-02662-2

Jin, Du, Xu, Deng, Liu et al., Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors, Nature, doi:10.1038/s41586-020-2223-y

Ka Ńtoch, Litwi Ńska, Szkoda, Siennicka, Importance of vitamin A deficiency in pathology and immunology of viral infections, Rocz. Panstw. Zakl. Hig

Kandeel, Al-Nazawi, Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease, Life Sci, doi:10.1016/j.lfs.2020.117627

Katsarou, Papasavva, Latsi, Drakoulis, Hemochromatosis: Hereditary Hemochromatosis and HFE Gene

Kaur, Henry, Micronutrient Status in Type 2 Diabetes: A review

Kehoe, Walton, Flynn, Nutritional challenges for older adults in Europe: Current status and future directions, Proc. Nutr. Soc, doi:10.1017/S0029665118002744

Kieliszek, Lipinski, Selenium supplementation in the prevention of coronavirus infections (COVID-19), Med. Hypotheses, doi:10.1016/j.mehy.2020.109878

Kobylecki, Afzal, Nordestgaard, Genetically high plasma vitamin C and urate: A Mendelian randomization study in 106 147 individuals from the general population, Rheumatology

Kuras, Reszka, Wieczorek, Jablonska, Gromadzinska et al., Biomarkers of selenium status and antioxidant effect in workers occupationally exposed to mercury, J. Trace Elem. Med. Biol, doi:10.1016/j.jtemb.2018.04.032

Kämpe, Enlund-Cerullo, Valkama, Holmlund-Suila, Rosendahl et al., Genetic variation in GC and CYP2R1 affects 25-hydroxyvitamin D concentration and skeletal parameters: A genome-wide association study in 24-month-old Finnish children, PLoS Genet, doi:10.1371/journal.pgen.1008530

Lietz, Oxley, Leung, Hesketh, Single nucleotide polymorphisms upstream from the β-carotene 15,15 -monoxygenase gene influence provitamin a conversion efficiency in female volunteers, J. Nutr, doi:10.3945/jn.111.140756

Lima, Ma, Winkler, Chu, Loh et al., A human microprotein that interacts with the mRNA decapping complex, Nat. Chem. Biol, doi:10.1038/nchembio.2249

Maggini, Feeding the immune system: The role of micronutrients in restoring resistance to infections, CAB Rev. Perspect. Agric. Vet. Sci. Nutr. Nat. Resour, doi:10.1079/PAVSNNR20083098

Maggini, Wintergerst, Beveridge, Hornig, Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses, Br. J. Nutr, doi:10.1017/S0007114507832971

May, The SLC23 family of ascorbate transporters: Ensuring that you get and keep your daily dose of vitamin C, Br. J. Pharmacol, doi:10.1111/j.1476-5381.2011.01350.x

Mclaren, Garner, Constantine, Mclachlan, Vulpe et al., Genome-wide association study identifies genetic loci associated with iron deficiency, PLoS ONE, doi:10.1371/journal.pone.0017390

Mensink, Fletcher, Gurinovic, Huybrechts, Lafay et al., Mapping low intake of micronutrients across Europe, Br. J. Nutr, doi:10.1017/S000711451200565X

Minandri, Imperi, Frangipani, Bonchi, Visaggio et al., Role of iron uptake systems in pseudomonas aeruginosa virulence and airway infection, Infect. Immun, doi:10.1128/IAI.00098-16

Mondul, Yu, Wheeler, Zhang, Weinstein et al., Genome-wide association study of circulating retinol levels, Hum. Mol. Genet, doi:10.1093/hmg/ddr387

Moy, Mondul, Zhang, Weinstein, Wheeler et al., Genome-wide association study of circulating vitamin D-binding protein, Am. J. Clin. Nutr, doi:10.3945/ajcn.113.080309

Moyersoen, Devleesschauwer, Dekkers, De Ridder, Tafforeau et al., Intake of fat-soluble vitamins in the belgian population: Adequacy and contribution of foods, fortified foods and supplements, Nutrients, doi:10.3390/nu9080860

Nda, Panel On Dietetic Products, Dietary reference values for vitamin D, EFSA J, doi:10.2903/j.efsa.2016.4547

Nda, Panel On Dietetic Products, Scientific opinion on dietary reference values for zinc, EFSA J, doi:10.2903/j.efsa.2014.3844

Nda, Panel On Dietetic Products, Scientific opinion on principles for deriving and applying dietary reference values, EFSA J, doi:10.2903/j.efsa.2010.1458

Nda, Panel On Dietetic Products, Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), EFSA J, doi:10.2903/j.efsa.2012.2815

Nongmaithem, Joglekar, Krishnaveni, Sahariah, Ahmad et al., GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians, Hum. Mol. Genet, doi:10.1093/hmg/ddx071

Opinion, Scientific opinion on dietary reference values for cobalamin (vitamin B12), EFSA J

Opinion, Scientific opinion on the substantiation of health claims related to copper and protection of DNA, proteins and lipids from oxidative damage (ID 263, 1726), function of the immune system (ID 264), maintenance of connective tissues, EFSA J, doi:10.2903/j.efsa.2009.1211

Opinion, Scientific opinion on the substantiation of health claims related to selenium and protection of DNA, proteins and lipids from oxidative damage, doi:10.2903/j.efsa.2009.1220

Opinion, Scientific opinion on the substantiation of health claims related to vitamin B6 and protein and glycogen metabolism (ID 65, 70, 71), function of the nervous system (ID 66), red blood, doi:10.2903/j.efsa.2009.1225

Opinion, Scientific opinion on the substantiation of health claims related to zinc and function of the immune system (ID 291, 1757), DNA synthesis and cell division (ID 292, 1759), protection of DNA, proteins and lipids from oxidative damage (ID 294, EFSA J, doi:10.2903/j.efsa.2009.1229

Panel, Nda, Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular functi, EFSA J, doi:10.2903/j.efsa.2010.1468

Panel, Nda, Scientific opinion on dietary reference values for copper, EFSA J, doi:10.2903/j.efsa.2015.4253

Panel, Nda, Scientific opinion on dietary reference values for folate, EFSA J, doi:10.2903/j.efsa.2014.3844

Panel, Nda, Scientific opinion on dietary reference values for iron, EFSA J, doi:10.2903/j.efsa.2015.4254

Panel, Nda, Scientific opinion on dietary reference values for selenium, EFSA J

Panel, Nda, Scientific opinion on dietary reference values for vitamin C 1, EFSA J

Panel, Nda, Scientific opinion on the substantiation of a health claim related to vitamin D and contribution to the normal function of the immune system pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA J, doi:10.2903/j.efsa.2015.4096

Panel, Nda, Scientific opinion on the substantiation of health claims related to copper and reduction of tiredness and fatigue (ID 272), maintenance of the normal function of the nervous system (ID 1723), maintenance of the normal function of the immune system (ID 17), EFSA J, doi:10.2903/j.efsa.2011.2079

Panel, Nda, Scientific opinion on the substantiation of health claims related to iron and formation of red blood cells and haemoglobin (ID 249, ID 1589), oxygen transport (ID 250, ID 254, ID 256, EFSA J, doi:10.2903/j.efsa.2009.1215

Percival, Copper and immunity, Am. J. Clin. Nutr, doi:10.1093/ajcn/67.5.1064S

Perricone, Bartoloni, Bursi, Cafaro, Guidelli et al., COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy, Immunol. Res, doi:10.1007/s12026-020-09145-5

Pichler, Minelli, Sanna, Tanaka, Schwienbacher et al., Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels, Hum. Mol. Genet, doi:10.1093/hmg/ddq552

Pilling, Tamosauskaite, Jones, Wood, Jones et al., Common conditions associated with hereditary haemochromatosis genetic variants: Cohort study in UK biobank, BMJ, doi:10.1136/bmj.k5222

Raffield, Louie, Sofer, Jain, Ipp et al., Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): Potential genomic intersection of iron and glucose regulation?, Hum. Mol. Genet, doi:10.1093/hmg/ddx082

Raha, Mallick, Basak, Duttaroy, Is copper beneficial for COVID-19 patients?, Med. Hypotheses, doi:10.1016/j.mehy.2020.109814

Razzaque, COVID-19 pandemic: Can maintaining optimal zinc balance enhance host resistance?, Tohoku J. Exp. Med, doi:10.1620/tjem.251.175

Rippin, Hutchinson, Jewell, Breda, Cade, Adult nutrient intakes from current national dietary surveys of European populations, Nutrients, doi:10.3390/nu9121288

Rocha, De Assis, Curcumin as a potential treatment for COVID-19, Phyther. Res

Rogero, Leão, Santana, Pimentel, Carlini et al., Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19, Free Radic. Biol. Med, doi:10.1016/j.freeradbiomed.2020.07.005

Rousseau, Kyomugasho, Celus, Hendrickx, Grauwet, Barriers impairing mineral bioaccessibility and bioavailability in plant-based foods and the perspectives for food processing, Crit. Rev. Food Sci. Nutr, doi:10.1080/10408398.2018.1552243

Ruan, Yang, Wang, Jiang, Song, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensiv, Care Med, doi:10.1007/s00134-020-05991-x

Saeed, Nadeem, Ahmed, Tahir Nadeem, Arshad et al., Studying the impact of nutritional immunology underlying the modulation of immune responses by nutritional compounds-A review, Food Agric. Immunol, doi:10.1080/09540105.2015.1079600

Sassi, Tamone, D'amelio, Vitamin, Nutrient, hormone, and immunomodulator, Nutrients, doi:10.3390/nu10111656

Satia, King, Morris, Stratton, White, Toenail and plasma levels as biomarkers of selenium exposure, Ann. Epidemiol, doi:10.1016/j.annepidem.2005.02.011

Seale, Torres, Berry, Pitts, A role for selenium-dependent GPX1 in SARS-CoV-2 virulence, Am. J. Clin. Nutr, doi:10.1093/ajcn/nqaa177

Semba, Vitamin A and immunity to viral, bacterial and protozoan infections, Proc. Nutr. Soc, doi:10.1017/S0029665199000944

Shane, Pangilinan, Mills, Fan, Gong et al., The 677C→T variant of MTHFR is the major genetic modifier of biomarkers of folate status in a young, healthy Irish population, Am. J. Clin. Nutr, doi:10.1093/ajcn/nqy209

Sheybani, Dokoohaki, Negahdaripour, Dehdashti, Zolghadr et al., The Role of Folic Acid in the Management of Respiratory Disease Caused by COVID-19, ChemRxiv, doi:10.26434/chemrxiv

Simonson, Vitamin C and coronavirus, Geriatr. Nurs, doi:10.1016/j.gerinurse.2020.05.002

Singh, Gupta, Kazmi, Al-Abbasi, Negi et al., SARS CoV-2 aggravates cellular metabolism mediated complications in COVID-19 infection, Dermatol. Ther, doi:10.1111/dth.13871

Sobczak, Stefanowicz, Pitt, Ajjan, Stewart, Total plasma magnesium, zinc, copper and selenium concentrations in type-I and type-II diabetes, BioMetals, doi:10.1007/s10534-018-00167-z

Sobiecki, Appleby, Bradbury, Key, High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: Results from the European prospective investigation into cancer and Nutrition-Oxford study, Nutr. Res, doi:10.1016/j.nutres.2015.12.016

Sthda-Home, None

Stockman, Bellamy, Garner, SARS: Systematic review of treatment effects, PLoS Med, doi:10.1371/journal.pmed.0030343

Strahle, Handley, Prediction of combustion induced vibration in rocket motors, Cell Host Microbe, doi:10.1016/j.chom.2013.04.010

Stubbs, Koutnik, Goldberg, Upadhyay, Turnbaugh et al., Investigating ketone bodies as immunometabolic countermeasures against respiratory viral infections, Med, doi:10.1016/j.medj.2020.06.008

Tanaka, Scheet, Giusti, Bandinelli, Piras et al., Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations, Am. J. Hum. Genet, doi:10.1016/j.ajhg.2009.02.011

Thomas-Valdés, Tostes, Anunciação, Da Silva, Sant'ana, Association between vitamin deficiency and metabolic disorders related to obesity, Crit. Rev. Food Sci. Nutr, doi:10.1080/10408398.2015.1117413

Timpson, Forouhi, Brion, Harbord, Cook et al., Erratum: Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): Evidence from 5 independent studies with > 15,000 participant, American Journal of Clinical Nutrition

Topilski, Flaishon, Naveh, Harmelin, Levo et al., The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cellsin vivo are due in part to the control of integrin-mediated T lymphocyte homing, Eur. J. Immunol, doi:10.1002/eji.200324532

Toti, Oliver Chen, Palmery, Valencia, Peluso, Non-provitamin A and provitamin A carotenoids as immunomodulators: Recommended dietary allowance, therapeutic index, or personalized nutrition?, Oxid. Med. Cell. Longev, doi:10.1155/2018/4637861

Trasino, A role for retinoids in the treatment of COVID-19?, Clin. Exp. Pharmacol. Physiol, doi:10.1111/1440-1681.13354

Troen, Mitchell, Sorensen, Wener, Johnston et al., Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women, J. Nutr, doi:10.1093/jn/136.1.189

Tuerk, Fazel, Zinc deficiency, Curr. Opin. Gastroenterol, doi:10.1097/MOG.0b013e328321b395

Van Doremalen, Bushmaker, Morris, Holbrook, Gamble et al., Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1, N. Engl. J. Med, doi:10.1056/NEJMc2004973

Van Meurs, Pare, Schwartz, Hazra, Tanaka et al., Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease, Am. J. Clin. Nutr, doi:10.3945/ajcn.112.044545

Vavougios, Selenium-Associated gene signatures within the SARS-CoV-2-Host genomic interaction interface, Free Radic. Biol. Med, doi:10.1016/j.freeradbiomed.2020.07.014

Velthuis, Van Den Worm, Sims, Baric, Snijder et al., Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture, PLoS Pathog, doi:10.1371/journal.ppat.1001176

Villamor, Mbise, Spiegelman, Hertzmark, Fataki et al., Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth, Pediatrics, doi:10.1542/peds.109.1.e6

Viñas, Ribas Barba, Ngo, Gurinovic, Novakovic et al., Projected prevalence of inadequate nutrient intakes in Europe, Ann. Nutr. Metab, doi:10.1159/000332762

Vural, Avery, Kalogiros, Coneyworth, Welham, Trace mineral intake and deficiencies in older adults living in the community and institutions: A systematic review, Nutrients, doi:10.3390/nu12041072

Wahedi, Ahmad, Abbasi, Stilbene-based natural compounds as promising drug candidates against COVID-19, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2020.1762743

Wallace, Combating COVID-19 and building immune resilience: A potential role for magnesium nutrition?, J. Am. Coll. Nutr, doi:10.1080/07315724.2020.1785971

Wang, Zhang, Richards, Kestenbaum, Van Meurs et al., Common genetic determinants of vitamin D insufficiency: A genome-wide association study, Lancet, doi:10.1016/S0140-6736(10)60588-0

Weir, Thenappan, Bhargava, Chen, Does vitamin D deficiency increase the severity of COVID-19?, Clin. Med, doi:10.7861/clinmed.2020-0301

Wishart, Increased micronutrient requirements during physiologically demanding situations: Review of the current evidence, Vitam. Miner, doi:10.4172/2376-1318.1000166

Wyss, Wirtz, Woggon, Brugger, Wyss et al., Expression pattern and localization of beta,beta-carotene 15,15 -dioxygenase in different tissues, Biochem. J, doi:10.1042/bj3540521

Xu, Yang, Chen, Luo, Zhang et al., Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system, Mol. Med. Rep, doi:10.3892/mmr.2017.7546

Zahedipour, Hosseini, Sathyapalan, Majeed, Jamialahmadi et al., Potential effects of curcumin in the treatment of COVID -19 infection, Phyther. Res, doi:10.1002/ptr.6738

Zhang, 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/nqaa095

Zhao, Huang, Dai, Feng, Liu et al., Serum iron level as a potential predictor of COVID-19 severity and mortality: A retrospective study, Open Forum Infect. Dis, doi:10.1093/ofid/ofaa250

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