Anti-Inflammatory and Antioxidant Response in COVID-19 Infection: Nrf2/HO-1 Pathway

Abstract

SARS-CoV-2 virus infection starts with the internalization of the viral particle into the host cells, mainly the upper respiratory system epithelial cells which have the highest expression of the ACE2 receptor which is essential for the internalization process. The pathophysiology of severe forms of COVID-19 disease results not only from direct, cytopathic viral effect but also from immune response dysregulation of the host resulting in hyperinflammatory state and oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2) ability to protect cells and induce a rapid anti-inflammatory and antioxidant response primarily depends on its constitutive cellular expression, which can be affected by numerous endogenous and exogenous factors. The binding of Nrf2 to cellular receptors leads to the transcription of a large number of genes encoding various antioxidant enzymes and other cytoprotective molecules, including heme oxygenase-1(HO-1). Activation of HO-1 results in antioxidant, anti-inflammatory and anti-apoptotic effects. Based on previous studies, the Nrf2/HO-1 pathway provides protection against oxidative stress and inflammatory and immune response which is significant in COVID-19 infection, which is characterized by a strong hyperinflammatory response. This narrative review aims to describe the role of the hyperinflammatory response in the development of COVID-19 infection, with a focus on the NrF2/HO-1 pathway.