Oxidative stress, antioxidant depletion, and DNA damage in post-COVID-19 patients: evidence of a disrupted redox network and loss of age-dependent antioxidant compensation

The relationship between oxidative stress and viral infections is well established, yet data on the redox consequences of COVID-19 beyond the acute phase remain sparse. We conducted a comprehensive assessment of oxidative stress biomarkers, antioxidant defences, and DNA damage in post-COVID patients, and examined whether COVID-19 infection disrupts the normal architecture of the antioxidant network. In this single-centre, cross-sectional, case–control study, 40 symptomatic post-COVID patients and 40 age- and sex-matched healthy controls were recruited from the Department of Respiratory Medicine, King George’s Medical University, Lucknow, India. Blood levels of lipid peroxidation (LPO), total antioxidant activity (TAA), superoxide dismutase (SOD), and glutathione reductase (GR) were measured. DNA damage was quantified using the alkaline comet assay. Data were analysed using Mann–Whitney U tests and Spearman rank correlations. Post-COVID patients showed profound antioxidant depletion: TAA was reduced by 60.8% (median 51.7 vs 224.3 mM; p < 0.001; Cohen’s d = 1.57), SOD by 34.0% (p < 0.001; d = 0.58), and GR by 35.0% (p < 0.001; d = 0.65). LPO was elevated but did not reach significance after correction for non-normality (p = 0.254), though it correlated significantly with radiographic severity (ρ = 0.403; p = 0.010) and was markedly elevated in patients with neurological involvement (2486.6 nmole/ml; p = 0.008). DNA damage was significantly increased across all comet parameters (% Tail DNA: + 24.0%; p < 0.001; d = 0.82). A novel finding was that the physiological age-dependent increase in TAA observed in controls (ρ = 0.425; p = 0.006) was abolished in patients (ρ = − 0.061; p = 0.707). Inter-marker correlation analysis revealed a rewiring of the antioxidant network, with breakdown of the normal LPO–TAA feedback relationship and emergence of SOD–TAA co-depletion. Post-COVID patients exhibit severe antioxidant depletion, significant DNA damage, and disruption of the normal redox network architecture. These findings provide a biochemical rationale for antioxidant-targeted therapeutic strategies in post-COVID management.