Role of Antioxidant Therapy in the Treatment and Prognosis of COVID-19: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: A significant aspect of the SARS-CoV-2 pathology involves oxidative stress, characterized by an imbalance between the production of harmful free radicals and the body's antioxidant defenses. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance.

OBJECTIVES: This systematic review and meta-analysis aimed to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2 infection.

METHODS: We searched the peer-reviewed indexed literature on MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, International Pharmaceutical Abstracts, and Scopus, from inception to July 2023.

RESULTS: The search identified 3306 articles from which 25 were included for quantitative synthesis, with 5 studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding intensive care unit admissions and hospital stays. Vitamin A studies indicated improvements in inflammatory markers. Vitamin C studies displayed inconsistent effects on clinical improvement and hospitalization. Combination treatments suggested benefits in symptom clearance and cytokine storm reduction. Meta-analysis of vitamin C studies found no significant difference in C-reactive protein concentrations (-0.50; 95% CI: -3.63, 2.63; I 2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I 2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I 2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: -2.37; 95% CI: -2.99, -1.76; I 2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias.

CONCLUSIONS: The review presents mixed efficacy of antioxidant therapies for SARS-CoV-2, with some studies indicating potential benefits. Further well-designed large-scale RCTs are warranted to determine the definitive role of antioxidants in SARS-CoV-2 treatment.This systematic review was registered at PROSPERO as CRD42023430805.