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 defences. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance. Objective This systematic review and meta-analysis aims to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2. 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 five studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding ICU 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 CRP levels (-0.50, 95%CI -3.63, 2.63; I2 = 0%), ICU stay duration (pooled MD 1.44, 95%CI 0.07, 2.81; I2 = 0%), or mortality (pooled OR 0.55, 95% CI 0.28, 1.09; I2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled MD -2.37, 95%CI: -2.99, -1.76; I2 = 49%). Of the 25 studies, eight were high quality with low bias, six had some concerns, and eleven were low quality with high bias. Conclusions The review presents mixed efficacy of antioxidant therapies of 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. Clinical trial registry This systematic review was registered with PROSPERO (registration number: CRD42023430805)