Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation
Beatrice Dufrusine, Silvia Valentinuzzi, Sandra Bibbò, Verena Damiani, Paola Lanuti, Damiana Pieragostino, Piero Del Boccio, Ersilia D’Alessandro, Alberto Rabottini, Alessandro Berghella, Nerino Allocati, Katia Falasca, Claudio Ucciferri, Francesco Mucedola, Marco Di Perna, Laura Martino, Jacopo Vecchiet, Vincenzo De Laurenzi, Enrico Dainese
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.