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

Abstract

BackgroundA 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. ObjectivesThis 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. MethodsWe 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. ResultsThe 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; I2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: −2.37; 95% CI: −2.99, −1.76; I2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias. ConclusionsThe 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.