Efficacy of Melatonin as an Adjunctive Therapy in Hospitalized Patients with Mild to Moderate COVID-19: A Randomized, Double-blind Clinical Trial

Background: Melatonin has proven antioxidant and anti-inflammatory properties that may address the pathophysiology of coronavirus disease 2019 (COVID-19). Therefore, the current study was conducted to evaluate the safety and efficacy of melatonin in COVID-19. Methods: In this single-center, randomized, double-blind, placebo-controlled clinical trial, 96 adults hospitalized with mild to moderate COVID-19 were recruited. The participants were allocated into the melatonin and the placebo groups, randomly (1:1 ratio). Results: The primary outcomes were a reduction in the length of hospital stay, the rate of ICU admissions, intubation/mechanical ventilation, and mortalities within 14 days of starting the treatment compared to the placebo group. After two weeks of follow-up, the blood oxygen saturation and the respiratory rate significantly improved in the melatonin group. C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, creatine phosphokinase, Ferritin, and D-dimer levels were significantly decreased in the melatonin group. Conversely, these markers were considerably increased in the placebo group. These serum marker levels also showed a significant difference in between- group comparison. The comparison of clinical endpoints between the two groups showed no significant difference. Conclusion: This clinical trial study indicated that the combination of oral melatonin tablets and standard treatment could substantially improve blood oxygen saturation and inflammatory factors in mild to moderate hospitalized COVID-19 patients.