Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Resultats clínics; ZincCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Resultados clínicos; ZincCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Clinical outcomes; ZincBackground: Zinc is an essential micronutrient that impacts host–pathogen interplay at infection. 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 an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. Methods: We ran an observational cohort 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 severe acute respiratory syndrome coronavirus 2 (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-CoV-2 infected cells. Interpretation: Low SZC is a risk factor that determines 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.This work was supported by the Spanish Ministry of Science and Innovation, through grants PID2019-106755RB-I00/AEI/10.13039/501100011033 to R.V. and PID2019-106959RB-I00/AEI/10.13039/501100011033 to J.D.; an institutional “Maria de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M) to R.V. and J.D.; 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 J.D. R.G.-F. 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))