New insights into extracellular and intracellular redox status in COVID-19 patients

Mohammad Javad Tavassolifar; Hamid Asadzadeh Aghdaei; Omid Sadatpour; Samaneh Maleknia; Sara Fayazzadeh; Seyed Reza Mohebbi; Fatemeh Montazer; Amirhassan Rabbani; Mohammad Reza Zali; Maryam Izad; Anna Meyfour

doi:10.1016/j.redox.2022.102563

New insights into extracellular and intracellular redox status in COVID-19 patients

Redox Biol. 2023 Feb:59:102563. doi: 10.1016/j.redox.2022.102563. Epub 2022 Dec 2.

Affiliations

¹ Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
³ Bioinformatics and Computational Omics Lab (BioCOOL), Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
⁴ Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁵ Department of Pathology, Firoozabadi Hospital, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
⁶ Department of Transplant & Hepatobiliary Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: izadm@sina.tums.ac.ir.
⁸ Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: a.meyfour@sbmu.ac.ir.

Abstract

Background: The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients.

Method: The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O₂^• - and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls.

Results: CAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O₂^• ^- were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance.

Conclusion: SARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising.

Keywords: COVID-19; Immune system; Nasopharyngeal; PBMCs; Redox system; SARS-COV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / genetics
Humans
Inflammation
Leukocytes, Mononuclear / metabolism
Oxidation-Reduction
Reactive Oxygen Species / metabolism
SARS-CoV-2 / metabolism

Substances

Reactive Oxygen Species