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..
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"abstract": "<jats:sec><jats:title>Introduction</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Serum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Median levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769).</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>The data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.</jats:p></jats:sec>",
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