Markers of Oxidative Stress in COVID-19: A Systematic Review of Biomarkers, Clinical Relevance, and Disease Severity Correlations

Background: Oxidative stress (OS) represents an imbalance between the production of reactive oxygen species (ROS) and the capacity of endogenous antioxidant defences to neutralize these radicals. SARS-CoV-2 infection triggers a profound redox imbalance, where reactive oxygen species (ROS) overwhelm antioxidant defenses, leading to cellular injury and complications like acute respiratory distress syndrome (ARDS). This systematic review evaluates the range, utility, and clinical relevance of oxidative stress (OS) biomarkers in assessing COVID-19 severity and outcomes. Methods: Adhering to PRISMA guidelines, we searched PubMed, Scopus, and Cochrane databases for studies published between January 2019 and October 2025. Following a rigorous screening of 7,602 articles, 23 studies were included based on their quantitative or qualitative assessment of OS markers in human COVID-19 patients across all levels of illness severity. Results: Findings consistently show that COVID-19 is associated with increased pro-oxidants and depleted antioxidant defenses. Malondialdehyde (MDA) and the OxLDL/LDL-C ratio emerged as reliable predictors of disease progression and mortality. Serum ROS and reactive nitrogen species (RNS) were significantly elevated, with the highest concentrations observed in ICU patients. Furthermore, severe cases frequently exhibited a profound deficiency of glutathione (GSH) and total thiols. However, results for antioxidant enzymes like SOD and CAT remained inconsistent across the literature. Conclusion: SARS-CoV-2 infection disrupts the host redox balance, leading to systemic oxidative stress and hyperinflammation, which significantly contributes to COVID-19 pathogenesis and links inflammation and coagulopathy to severe outcomes. Redox-dependent markers, including lipid oxidation products (MDA, OxLDL), protein oxidation products (AGEs), and indicators of compromised antioxidant capacity (GSH/thiols), demonstrate significant clinical utility in diagnosing and predicting the severity and mortality associated with COVID-19.