Dysregulation of Nrf2, Caspase-1, and Survivin in Peripheral Blood of Iranian Patients with Severe Covid-19: A qRT-PCR Analysis

Abstract

Background: SARS-CoV-2 can lead to both acute and chronic inflammation. Objectives: This study aims to investigate the expression levels of nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2), caspase-1, and BIRC5 in hospitalized patients with SARS-CoV-2. Methods: The expression levels of NRF2, caspase-1, and BIRC5 were evaluated in 100 individuals, comprising 70 hospitalized patients infected with SARS-CoV-2 and 30 uninfected individuals as a control group. All participants were in the initial stages of their illness, within 24 hours of experiencing symptoms, and had not yet received any treatment for SARS-CoV-2. The mRNA was extracted from blood samples, converted to cDNA, and analyzed using real-time PCR. Gene expression between groups was compared using the Mann-Whitney U test. Correlations between gene expression levels were assessed using Spearman's rank correlation coefficient. Results: The expression of caspase-1 was significantly higher in patients compared to healthy controls (P = 0.008). The median relative expression of BIRC5 was significantly lower in patients than in healthy controls (P < 0.001). The NRF2 expression showed a trend towards higher expression in infected patients, although the differences in NRF2 expression between the groups did not reach statistical significance (P = 0.081). Correlation analysis revealed statistically significant positive associations between BIRC5 and NEF2L2 (rs = 0.585, P < 0.001), between BIRC5 and caspase-1 (rs = 0.613, P < 0.001), and between caspase-1 and NEF2L2 (rs = 0.618, P < 0.001). Conclusions: The positive correlations observed among BIRC5, NRF2, and caspase-1 underscore the interconnectedness of these pathways in the inflammatory response to severe COVID-19. These findings contribute to our understanding of the molecular mechanisms underlying COVID-19 and may inform future therapeutic strategies aimed at modulating inflammation in affected patients.