Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: a case-control study
Antoine Equey, Mette M Berger, Semira Gonseth-Nusslé, Marc Augsburger, Serge Rezzi, Andrew C C Hodgson, Sandrine Estoppey, Giuseppe Pantaleo, Céline Pellaton, Maïwenn Perrais, Sébastien Lenglet, Valentin Rousson, Valérie D’acremont, Murielle Bochud
Clinical Nutrition, doi:10.1016/j.clnu.2023.04.007
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
subpopulations (normal ratio: 1:1).
Appendix
References
Abdallah, Mhalla, Trabelsi, Sekma, Youssef et al., Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial, Clin Infect Dis
Alwan, Pruijm, Ponte, Ackermann, Guessous et al., Epidemiology of masked and white-coat hypertension: the family-based SKIPOGH study, PLoS One
Bassatne, Basbous, Chakhtoura, El Zein, Rahme et al., The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis, Metabolism
Beck, Selenium and host defence towards viruses, Proceedings of the Nutrition Society
Ben-Eltriki, Hopefl, Wright, Deb, Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies, J Am Coll Nutr
Berger, Herter-Aeberli, Zimmermann, Spieldenner, Eggersdorfer, Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action, Clin Nutr ESPEN
Berger, Talwar, Shenkin, Pitfalls in the Interpretation of blood tests used to assess and monitor micronutrient nutritional status, Nutr Clin Pract
Brenner, Holleczek, Schottker, Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?, Nutrients
Burri, Haldimann, Dudler, Selenium status of the Swiss population: assessment and change over a decade, J Trace Elem Med Biol
Butty, Buhler, Pasquier, Dupraz, Faivre et al., Adherence to Coronavirus Disease 2019 Preventive Measures in a Representative Sample of the Population of the Canton of Vaud, Switzerland, Int J Public Health
Böckerman, Bryson, Viinikainen, Viikari, Lehtimäki et al., The serum copper/zinc ratio in childhood and educational attainment: a population-based study, J Public Health (Oxf)
Calder, Carr, Gombart, Eggersdorfer, Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections, Nutrients
Chasapis, Georgiopoulou, Perlepes, Bjorklund, Peana, A SARS-CoV-2 -human metalloproteome interaction map, J Inorg Biochem
Chillon, Maares, Demircan, Hackler, Sun et al., Serum Free Zinc Is Associated With Vaccination Response to SARS-CoV-2, Front Immunol
Collins, Copper nutrition and biochemistry and human (patho)physiology, Adv Food Nutr Res
D'ecclesiis, Gavioli, Martinoli, Raimondi, Chiocca et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis, PLoS One
Devi, Nandakishore, Sangeeta, Basar, Devi et al., Zinc in Human health, Journal of Dental and Medical Sciences (IOSR-JDMS
Dietz, Santos-Burgoa, Obesity and its Implications for COVID-19 Mortality, Obesity (Silver Spring
Dupraz, Butty, Duperrex, Estoppey, Faivre et al., Prevalence of SARS-CoV-2 in Household Members and Other Close Contacts of COVID-19 Cases: A Serologic Study in Canton of Vaud, Switzerland, Open Forum Infect Dis
El Ati-Hellal, Doggui, Hedhili, Traissac, El Ati, Zinc and copper status in childbearing age Tunisian women: Relation to age, residential area, socioeconomic situation and physiologic characteristics, Chemosphere
Engin, Engin, Engin, Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients?, Environ Toxicol Pharmacol
Ernährung E, Ernährung älterer Menschen in stationären Einrichtungen (ErnSTES-Studies)
Fenwick, Croxatto, Coste, Pojer, Andre et al., Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies, Clin Nutr
Giacconi, Costarelli, Piacenza, Basso, Rink et al., Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study, Eur J Nutr
Gombart, Pierre, Maggini, A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection, Nutrients
Goullé, Mahieu, Castermant, Neveu, Bonneau et al., Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values, Forensic Sci Int
Govind, Bharadwaj, Ganesh, Vishnu, Shankar et al., Antiviral properties of copper and its alloys to inactivate covid-19 virus: a review, Biometals
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D supplementation could reduce risk of Influenza and COVID-19 infections and deaths, Nutrients
Guessous, Dudler, Glatz, Theler, Zoller et al., Vitamin D levels and associated factors: a population-based study in Switzerland, Swiss Med Wkly
Hackler, Heller, Sun, Schwarzer, Diegmann et al., Human biomonitoring of 73 elements in blood, serum, erythrocytes and urine, J Trace Elem Med Biol
Havervall, Marking, Svensson, Greilert-Norin, Nilsson et al., Anti-Spike Mucosal IgA Protection against SARS-CoV-2 Omicron Infection, New Engl J Med
Heller, Sun, Hackler, Seelig, Seibert et al., Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker, Redox Biol
Herter-Aeberli, Graf, Vollenweider, Haberling, Srikanthan et al., Validation of a Food Frequency Questionnaire to Assess Intake of n-3 Polyunsaturated Fatty Acids in Switzerland, Nutrients
Hess, Peerson, King, Brown, Use of serum zinc concentration as an indicator of population zinc status, Food Nutr Bull
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab
Hosseini, El Abd, Ducharme, Kehoe, Walton et al., Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis, Proc Nutr Soc
Hunter, Arentz, Goldenberg, Yang, Beardsley et al., Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials, BMJ Open
J O U R N A L P R E, -p r o o f
J O U R N A L P R E, -p r o o f
Jenny-Burri, Haldimann, Dudler, Estimation of selenium intake in Switzerland in relation to selected food groups, Food Addit Contam Part A Chem Anal Control Expo Risk Assess
Jothimani, Kailasam, Danielraj, Nallathambi, Ramachandran et al., COVID-19: Poor outcomes in patients with zinc deficiency, Int J Infect Dis
Kheirouri, Alizadeh, Decreased serum and mucosa immunoglobulin A levels in vitamin A and zinc-deficient mice, Cent Eur J Immunol
Kitamura, Morikawa, Kamon, Iguchi, Hojyo et al., Toll-like receptormediated regulation of zinc homeostasis influences dendritic cell function, Nat Immunol
Laine, Tuomainen, Salonen, Virtanen, Serum copper-to-zinc-ratio and risk of incident infection in men: the Kuopio Ischaemic Heart Disease Risk Factor Study, Eur J Epidemiol
Laing, Petrovic, Lachat, De Boevre, Klingenberg et al., Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission, Nutrients
Li, Luo, Liang, Circulating trace elements status in COVID-19 disease: A meta-analysis, Front Nutr
Maares, Haase, Zinc and immunity: An essential interrelation, Arch Biochem Biophys
Maares, Hackler, Haupt, Heller, Bachmann et al., Free Zinc as a Predictive Marker for COVID-19 Mortality Risk, Nutrients
Maggini, Pierre, Calder, Immune function and micronutrient requirements change over the life course, Nutrients
Majeed, Nagabhushanam, Prakasan, Mundkur, Bae et al., Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19, Int J Mol Sci
Malavolta, Piacenza, Basso, Giacconi, Costarelli et al., Serum copper to zinc ratio: Relationship with aging and health status, Mech Ageing Dev
Mironczuk, Kapica-Topczewska, Socha, Soroczynska, Jamiolkowski et al., Copper, Zinc Concentrations and Cu/Zn, Cu/Se Molar Ratios in the Serum of Patients with Acute Ischemic Stroke in Northeastern Poland-A New Insight into Stroke Pathophysiology, BMC Childbirth
Moghaddam, Heller, Sun, Seelig, Cherkezov et al., Selenium Deficiency Is Associated with Mortality Risk from COVID-19, Biol Trace Elem Res
Morante, Penna, Rossi, Stellato, SARS-CoV-2 virion stabilization by Zn binding, Front Mol Biosci
Nève, Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity, J Trace Elements Med Biol
Oristrell, Oliva, Casado, Subirana, Dominguez et al., Vitamin D supplementation and COVID-19 risk: a population-based, cohort study, J Endocrinol Invest
Osredkar, Sustar, Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance, J Clinic Toxicol
Perrais, Thomas, Augsburger, Lenglet, Comparison of Dried Blood Spots and Microtubes Techniques for Traces Elements Quantification by ICP-MS, J Anal Toxicol
Pilette, Ouadrhiri, Godding, Vaerman, Sibille, Lung mucosal immunity: immunoglobulin-A revisited, Eur Respir J
Prasad, Lessons Learned from Experimental Human Model of Zinc Deficiency, J Immunol Res
Pruijm, Ponte, Ackermann, Paccaud, Guessous et al., Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population, Clin J Am Soc Nephrol
Raha, Mallick, Basak, Duttaroy, Is copper beneficial for COVID-19 patients?, Med Hypotheses
Rousson, Ackermann, Ponte, Pruijm, Guessous et al., Sex-and agespecific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults, PLoS One
Sadeghsoltani, Mohammadzadeh, Safari, Hassanpour, Izadpanah et al., Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation, Biol Trace Elem Res
Schottker, Ball, Gellert, Brenner, Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies, Ageing Res Rev
Schupbach, Wegmuller, Berguerand, Bui, Herter-Aeberli, Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland, Eur J Nutr
Schöttker, Haug, Schomburg, Kohrle, Perna et al., Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study, Am J Clin Nutr
Sintzel, Rametta, Reder, Vitamin D and Multiple Sclerosis: A Comprehensive Review, Neurol Ther
Skalny, Rink, Ajsuvakova, Aschner, Gritsenko et al., Zinc and respiratory tract infections: Perspectives for COVID-19 (Review), Int J Mol Med
Stroehlein, Wallqvist, Iannizzi, Mikolajewska, Metzendorf et al., Vitamin D supplementation for the treatment of COVID-19: a living systematic review, Cochrane Database Syst Rev
Thomas, Patel, Bittel, Wolski, Wang 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
Tianbing, Zhe, Fengxue, Zhaolong, Youzhong et al., Comorbidities and multi-organ injuries in the treatment of COVID-19, The Lancet
Troesch, Eggersdorfer, Weber, The role of vitamins in aging societies, Int J Vitam Nutr Res
Velthuis, Van Den Worm, Sims, Baric, Snijder et al., 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
Vlieg-Boerstra, De, Meyer, Agostoni, De Cosmi et al., Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis, Allergy
Voelkle, Gregoriano, Neyer, Koch, Kutz et al., Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study, Nutrients
Vogel-González, Talló-Parra, Herrera-Fernández, Pérez-Vilaró, Chillón et al., Low Zinc levels at clinical admission associates with poor outcomes in COVID-19 in SARS-CoV-2 infection, Nutrients
Wessels, Rolles, Rink, The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis, Front Immunol
Wessels, Rolles, Slusarenko, Rink, Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of COVID-19, Brit J Nutr
West, Anker, Amati, Richard, Wisniak et al., Corona Immunitas: study protocol of a nationwide program of SARS-CoV-2 seroprevalence and seroepidemiologic studies in Switzerland, Int J Public Health
Zhang, Taylor, Bennett, Saad, Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, Am J Clin Nutr
{ 'indexed': {'date-parts': [[2023, 4, 19]], 'date-time': '2023-04-19T05:48:59Z', 'timestamp': 1681883339258},
'reference-count': 0,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2023, 4, 1]],
'date-time': '2023-04-01T00:00:00Z',
'timestamp': 1680307200000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2023, 4, 7]],
'date-time': '2023-04-07T00:00:00Z',
'timestamp': 1680825600000},
'content-version': 'vor',
'delay-in-days': 6,
'URL': 'http://creativecommons.org/licenses/by/4.0/'}],
'content-domain': { 'domain': [ 'clinicalkey.fr', 'clinicalkey.jp', 'clinicalkey.es', 'clinicalkey.com.au',
'clinicalkey.com', 'clinicalnutritionjournal.com', 'elsevier.com',
'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2023, 4]]},
'DOI': '10.1016/j.clnu.2023.04.007',
'type': 'journal-article',
'created': {'date-parts': [[2023, 4, 18]], 'date-time': '2023-04-18T08:03:59Z', 'timestamp': 1681805039000},
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general '
'population: a case-control study',
'prefix': '10.1016',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-5434-2477',
'authenticated-orcid': False,
'given': 'Antoine',
'family': 'Equey',
'sequence': 'first',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-5427-1648',
'authenticated-orcid': False,
'given': 'Mette M.',
'family': 'Berger',
'sequence': 'additional',
'affiliation': []},
{'given': 'Semira', 'family': 'Gonseth-Nusslé', 'sequence': 'additional', 'affiliation': []},
{'given': 'Marc', 'family': 'Augsburger', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-0691-2153',
'authenticated-orcid': False,
'given': 'Serge',
'family': 'Rezzi',
'sequence': 'additional',
'affiliation': []},
{'given': 'Andrew C.C.', 'family': 'Hodgson', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-3067-7584',
'authenticated-orcid': False,
'given': 'Sandrine',
'family': 'Estoppey',
'sequence': 'additional',
'affiliation': []},
{'given': 'Giuseppe', 'family': 'Pantaleo', 'sequence': 'additional', 'affiliation': []},
{'given': 'Céline', 'family': 'Pellaton', 'sequence': 'additional', 'affiliation': []},
{'given': 'Maïwenn', 'family': 'Perrais', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sébastien', 'family': 'Lenglet', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-8092-4446',
'authenticated-orcid': False,
'given': 'Valentin',
'family': 'Rousson',
'sequence': 'additional',
'affiliation': []},
{'given': 'Valérie', 'family': 'D’Acremont', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-5727-0218',
'authenticated-orcid': False,
'given': 'Murielle',
'family': 'Bochud',
'sequence': 'additional',
'affiliation': []}],
'member': '78',
'container-title': 'Clinical Nutrition',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S0261561423001139?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S0261561423001139?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2023, 4, 18]],
'date-time': '2023-04-18T08:04:05Z',
'timestamp': 1681805045000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S0261561423001139'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2023, 4]]},
'references-count': 0,
'alternative-id': ['S0261561423001139'],
'URL': 'http://dx.doi.org/10.1016/j.clnu.2023.04.007',
'relation': {},
'ISSN': ['0261-5614'],
'subject': ['Critical Care and Intensive Care Medicine', 'Nutrition and Dietetics'],
'container-title-short': 'Clinical Nutrition',
'published': {'date-parts': [[2023, 4]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA '
'seropositivity in the general population: a case-control study',
'name': 'articletitle',
'label': 'Article Title'},
{'value': 'Clinical Nutrition', 'name': 'journaltitle', 'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.clnu.2023.04.007',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2023 The Author(s). Published by Elsevier Ltd.',
'name': 'copyright',
'label': 'Copyright'}]}
