Abstract: Biological Trace Element Research https://doi.org/10.1007/s12011-022-03124-7 Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS‑CoV‑2 Patients Kiran Kumar PVSN1 · Sojit Tomo1 · Purvi Purohit1 · Shrimanjunath Sankanagoudar1 · Jayakaran Charan2 · Abhishek Purohit3 · Vijaylakshami Nag4 · Pradeep Bhatia5 · Kuldeep Singh6 · Naveen Dutt7 · Mahendra Kumar Garg8 · Praveen Sharma1 · Sanjeev Misra9 · Dharamveer Yadav1 Received: 21 December 2021 / Accepted: 17 January 2022 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract The deficiencies of trace elements and infectious diseases often coexist and exhibit complex interactions. Several trace elements such as zinc (Zn), copper (Cu) and magnesium (Mg) have immunomodulatory functions and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of trace metals in association with severity and mortality in SARS-CoV-2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Zn, Mg and Cu levels were analysed by direct colourimetric method. Both serum Cu and Zn levels were significantly decreased in cases when compared to those in controls (p < 0.005 and p < 0.0001). Serum magnesium levels although not significant were found to be slightly decreased in controls. On comparing the trace elements between the deceased and discharged cases, a significant difference was found between serum copper and zinc levels, but for magnesium, both groups have similar levels. The receiver operating characteristic (ROC) curve results indicate that a serum Cu/Zn ratio along with the age of patient provides some reliable information on COVID-19 course and survival odds by yielding an AUC of 95.1% with a sensitivity of 93.8% and specificity of 89.8%. Therefore, we would like to emphasize that measuring the serum copper and zinc along with their ratio can be used as routine investigations for COVID-19 patients in proper identification and management of severe cases in upcoming new waves of COVID-19. Keywords Trace metals · Copper · Zinc · Magnesium · COVID-19