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Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation
Beatrice Dufrusine1,2,3, Silvia Valentinuzzi3,4, Sandra Bibbò2,3
1Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy.
Insights
This study reveals altered iron metabolism and activated 5-lipoxygenase (5-LOX) in COVID-19 and long-COVID patients. Leukotriene B4 (LTB4) and lipocalin 2 (LCN2) are identified as potential biomarkers for disease management.
Area of Science:
- Immunology
- Biochemistry
- Molecular Biology
Background:
- Coronavirus disease 2019 (COVID-19) presents with diverse symptoms, and some patients develop long-term post-COVID-19 syndrome (long-COVID).
- Understanding the molecular underpinnings of COVID-19 and long-COVID is crucial for effective patient management and therapeutic development.
Purpose of the Study:
- To investigate the molecular and functional mechanisms in COVID-19 and long-COVID.
- To identify potential biomarkers for managing patients with acute COVID-19 and long-COVID.
Main Methods:
- Proteomic analysis of lymphocytes from COVID-19 and long-COVID patients.
- Biochemical assays to assess iron metabolism proteins: ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1).
- Evaluation of 5-lipoxygenase (5-LOX) activation and its potential iron-dependent post-translational regulation.
Main Results:
- Significant alterations in proteins associated with iron metabolism were observed in COVID-19 and long-COVID patients.
- Activation of 5-lipoxygenase (5-LOX) was detected in both COVID-19 and long-COVID, potentially mediated by an iron-dependent mechanism.
- Leukotriene B4 (LTB4) and lipocalin 2 (LCN2) were identified as potential biomarkers for COVID-19 and long-COVID.
Conclusions:
- Iron metabolism dysregulation and 5-LOX activation are key molecular events in COVID-19 and long-COVID.
- LTB4 and LCN2 show promise as diagnostic or prognostic markers for COVID-19 and long-COVID.
- The findings suggest new avenues for the prevention and treatment of COVID-19 and its long-term sequelae.
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.
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