Oxidative stress and decreased Nrf2 level in pediatric patients with COVID‐19

Abstract

The aim of this study was to investigate the change in nuclear factor erythroid 2-related factor (Nrf2), which plays a critical role in cytoprotection against oxidative stress, in pediatric patients with coronavirus disease 2019 (COVID-19) infection positivity, and to evaluate the relationship between Nrf2 and oxidative balance. The study included 40 children with confirmed COVID-19 infection and 35 healthy children. The groups were compared in respect of Nrf2, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), in addition to clinical findings of fever, cough, shortness of breath, contact history, and demographic data of age and gender. The mean Nrf2 values and TAS levels were determined to be statistically significantly low (p < 0.001) and the TOS level and OSI were statistically significantly high in the children with COVID-19 compared to the control group. A significant positive correlation was determined between Nrf2 and TAS (p < 0.01); as the Nrf2 value increased, so the TAS value increased. A significant negative correlation was determined between Nrf2 and TOS and OSI (p < 0.01); as the Nrf2 value increased, there was determined to be a significant decrease in the TOS and OSI values. COVID-19 infection in pediatric patients causes a decrease in the Nrf2 level.

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

“…Moreover, infection of Vero hTMPRSS2 cells with SARS-CoV-2 decreased levels of Heme Oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) induced by Nrf2 [ 62 ]. In children with COVID-19, decreased levels of Nrf2 with reduced total antioxidant status and increased total oxidant status and oxidative stress index were observed [ 63 ]. Increased levels of ROS and H 2 O 2 trigger inflammasome as a significant player in cytokine storm-related to severe forms of COVID-19.…”

“…Besides increased oxidative stress in COVID-19 patients, decreased antioxidant capacity was observed [ 34 ]. As discussed in other parts of this article, some of the main reasons for decreased antioxidant capacity could be the inactivation of the Nrf2 transcription factor and decrease in antioxidant proteins controlled by Nrf2 [ 62 , 63 ], as well as alterations in the activity of crucial antioxidant enzymes and processes such as GPX with GSH [ 30 , 31 , 75 , 76 , 78 , 79 , 87 , 94 , 98 ], and PON-1 [ 81 ].…”

How to Restore Oxidative Balance That Was Disrupted by SARS-CoV-2 Infection

“…Klf9 further stimulates ROS production by repressing NRF2 target genes, such as thioredoxin reductase 2 ( Txnrd2), with antioxidant activity ( Figure 4 ) [ 66 ]. Gümüs, H et al demonstrated that SARS-CoV-2 infection decreases the level of NRF2 [ 67 ]. One of the treatment agents that activates NRF2 is dimethyl fumarate (DMF), typically used to treat multiple sclerosis.…”

Antioxidant Effects of Dietary Supplements on Adult COVID-19 Patients: Why Do We Not Also Use Them in Children?

“…The study showed a decreased level of Nrf2 that was correlated to a decreased total antioxidant status, with a contextual increase in total oxidant status (TOS) and OS index (OSI) compared to the control group. The decrease in Nrf2 levels, through an increase in ROS production, might explain the lung tissue damage related to COVID-19; moreover, the more symptomatic the child was, the higher the TOS and OSI values were [ 26 ]. In particular, reduced Nrf2 levels were associated with bronchopulmonary inflammation, epithelial damage and mucous cell metaplasia [ 26 ].…”

“…The decrease in Nrf2 levels, through an increase in ROS production, might explain the lung tissue damage related to COVID-19; moreover, the more symptomatic the child was, the higher the TOS and OSI values were [ 26 ]. In particular, reduced Nrf2 levels were associated with bronchopulmonary inflammation, epithelial damage and mucous cell metaplasia [ 26 ]. An antioxidant diet, rich in vegetables (i.e., broccoli), can have a clinical benefit, although in clinical cases of SARS-CoV-2 affected patients who were given broccoli capsules, the clinical benefit was partial [ 24 ].…”