Pathophysiological Complications of Persistent Oxidative Stress Following COVID-19

Abstract

Background: Persistent oxidative stress may contribute substantially to post-COVID-19 complications through sustained inflammation, endothelial dysfunction, mitochondrial impairment, lipid peroxidation and depletion of antioxidant defenses. However, the relationship between persistent redox imbalance and multisystem pathophysiological consequences following recovery from COVID-19 remains incompletely characterized. The present study evaluated oxidative stress biomarkers and their association with pulmonary, cardiovascular, metabolic and functional complications following SARS-CoV-2 infection.

Methods: A comparative cross-sectional study was conducted among 120 adults, comprising 80 individuals with persistent post-COVID-19 symptoms 3–12 months after laboratory-confirmed SARS-CoV-2 infection and 40 age- and sex-matched healthy controls. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), C-reactive protein (CRP), interleukin-6 (IL-6), fasting glucose and lipid profile were measured. Oxidative Stress Index (OSI) was calculated as TOS/TAC ×100. Pulmonary function was assessed using spirometry, while persistent fatigue, dyspnea and exercise intolerance were documented using standardized clinical assessment. Comparisons were performed using independent t-test or Mann–Whitney U test, and correlations were assessed using Pearson/Spearman correlation analysis.

Results: Post-COVID-19 participants demonstrated significantly greater oxidative stress than healthy controls, with higher MDA (4.82±1.21 vs. 2.91±0.74 nmol/mL), TOS (38.6±9.4 vs. 21.8±5.7 µmol H₂O₂ equivalent/L) and OSI (5.74±1.82 vs. 2.61±0.83; all p<0.001). TAC was significantly reduced (0.67±0.16 vs. 1.04±0.21 mmol Trolox equivalent/L), accompanied by lower SOD (71.4±15.8 vs. 96.7±18.3 U/mL), CAT (42.8±9.7 vs. 58.9±11.4 U/mL) and GSH (4.21±1.03 vs. 6.18±1.24 µmol/L; all p<0.001). Inflammatory markers were also significantly elevated, including CRP (6.8±3.4 vs. 2.1±1.2 mg/L) and IL-6 (8.7±4.1 vs. 3.2±1.4 pg/mL; p<0.001). Among post-COVID participants, 46.3% had persistent dyspnea, 52.5% reported fatigue and 31.3% demonstrated reduced pulmonary function. OSI showed positive correlations with CRP (r=0.61), IL-6 (r=0.57), MDA (r=0.68) and severity of dyspnea (r=0.49), while TAC correlated inversely with CRP (r=-0.52) and fatigue scores (r=-0.45) (p<0.001 for all). Participants with high OSI had a 3.42-fold greater likelihood of persistent functional complications than those with lower OSI (95% CI: 1.58–7.39; p=0.002).

Conclusion: Persistent oxidative stress following COVID-19 is associated with substantial depletion of antioxidant defenses, increased lipid peroxidation and sustained systemic inflammation. The strong relationship between oxidative imbalance and pulmonary as well as functional complications suggests that persistent redox dysregulation may represent an important pathophysiological mechanism underlying post-COVID-19 morbidity. Oxidative stress biomarkers, particularly OSI, MDA and TAC, may have potential utility for identifying individuals at increased risk of persistent post-COVID complications and may provide targets for future therapeutic interventions.