Dysregulation of redox-inflammatory markers in COVID-19: a multi-parameter analysis with disease severity

Viral infections are one of the biggest threats ever known to humankind. Viral mutability against the human defense system makes them deadly. Virus manipulates host gene expressions, dictating the course of the disease using inflammation-induced oxidative stress. Characterized by uncontrolled Reactive oxygen species levels and weakened antioxidant defenses, which significantly impact viral disease severity. SARS-CoV-2, a constant threat due to its ability to mutate, showcases this interplay, emphasizing the need to understand host cellular responses. Unraveling these viral modulation patterns offers insight into predicting disease severity and identifying therapeutic targets. The study used infected groups (Severe, Moderate, and Mild) and a control group. The samples were collected using a non-probability stratified sampling approach and were collected early after diagnosis to minimize treatment-related variability: at hospitalization for severe cases, within 12 hours of clinic visit for moderate cases, and within 24 hours of RT-PCR confirmation for mild cases. Disease severity classification was performed by clinicians based on clinical symptoms and oxygen saturation (SpO₂). This research delves into assessing the intricate interplay between the severity of the viral infection and inflammation-induced redox imbalance by expression profile of key antioxidant genes (GPx, NRF2, SOD2), pro-inflammatory genes (ACE2, NOS2), and RNA-binding gene (HuR), by comparing the total hydroperoxides as an indirect markeer for ROS, serum Ang II levels, and clinical data among the groups infected individuals. Significant expressional dysregulation of proinflammatory, oxidative, and anti-oxidative markers is found among the study groups, especially in the severe group. ACE2, GPx, and SOD2 were downregulated, while NOS2, HuR, and Nrf2 were upregulated, which indicates a shift towards a pro-oxidant state, such as twice the amount of ROS in both severe and moderate groups, and Serum Ang II levels are halved in the severe group. Clinical biomarkers were also elevated. These findings establish a strong correlation between redox-inflammatory dysregulation and the severity of infections.