Metallomic analysis of urine from individuals with and without Covid-19 infection reveals extensive alterations in metal homeostasis

Abstract Metal ions perform important functions in the body and their concentrations in cells and tissues are tightly controlled. Alterations in metal homeostasis can occur in certain disease states including infection. In this study urinary excretion of several metals including calcium, cadmium, cobalt, copper, iron, magnesium, nickel, selenium, and zinc in Covid-19 patients (n=35) and control (n=60) individuals, spanning ages and sexes. Urinary samples were analysed using ICP-MS and the differences in metal concentrations between the Covid-19-infected and control groups were assessed using multivariate data analysis and univariate data analysis employing Student's t-test and Pearson's correlation, with significance set at p<0.05. The urinary concentrations of all metals analysed were significantly higher in the Covid-infected group (compared to controls), with the exception of copper, which was markedly reduced. The increase in calcium excretion was lower and magnesium excretion greater in Covid-19-positive individuals aged 41 or over compared to those aged 40 or lower. Whilst the increase in iron excretion was lower, and cobalt excretion greater in Covid-19-positive males compared to females. The study highlights significant alterations in the handling of a range of metals in the body during Covid-19 infection. It also highlights both age and sex-specific differences in metal homeostasis. The results suggest an important role for copper in the body during Covid-19 infection and suggests that urinary concentrations of copper and other metals may serve as markers to predict progression of the disease.