Low Zinc Levels at Clinical Admission Associates with Poor Outcomes in COVID-19

Background: Biomarkers to predict Coronavirus disease-19 (COVID-19) outcome early at infection are urgently needed to improve prognosis and treatment. Zinc balances immune responses and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with more severe COVID-19 outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression and thus might represent a useful biomarker.Methods: We run a retrospective observational study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel we have studied SARS-CoV2 replication in the Vero E6 cell line modifying zinc concentrations.Findings: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dl at admission correlated with worse clinical presentation, longer time to reach stability and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV2 infected cells.Interpretation: SZC is a novel biomarker to predict COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.Funding: This work was supported by the Spanish Ministry of Science and Innovation through grants PID2019-106755RB-I00/AEI/10.13039/501100011033 to RV and PID2019-106959RB-I00/AEI /10.13039/501100011033 to JD, an institutional “Maria de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M) to RV and JD and by the 2017 SGR 909 grant from the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement of the Generalitat de Catalunya to JD. RGF received support and funding from Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) [Grant number CB16/10/00245], FEDER funds and the FIS Project from Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación [Grant number (PI19/00019)]Declaration of Interests: The authors declare that no competing interests exist.Ethics Approval Statement: The Institutional Ethics Committee of Hospital del Mar of Barcelona approved the study and due to the nature of the retrospective data review, and waived the need for informed consent from individual patients (CEIm 2020/9352).