The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis
MD, PhD a Xin-Chen Wang, Guang-Liang Wu, MD, PhD Ye-Feng Cai, MD, PhD Shi-Jie Zhang
Medicine, doi:10.1097/md.0000000000030874
Background: As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are respiratory symptoms, fever, cough, shortness of breath, and dyspnea, with multiple organ injuries in severe cases. Therefore, finding drugs to prevent and treat COVID-19 is urgently needed and expected by the public. Several studies suggested beneficial effects of melatonin for the relevant prevention and treatment. To explore the effect and safety of melatonin in the treatment and provide theoretical support and reference for seeking the most suitable drug for COVID-19, the meta-analysis was carried out accordingly. Methods: It included randomized clinical trials of patients with COVID-19 treated with melatonin. Total effective rate was the primary outcome, while C-reactive protein (CRP), arterial oxygen saturation (SaO 2 ), white blood cell count (WBC) were the secondary measures. Random-effect and fixed-effect models were used to evaluate the effect size of some indicators in this meta-analysis. Results: Six eligible studies with 338 participants were included. One hundred seventy subjects were treated with melatonin adjuvant therapy and 168 subjects were assigned to the control group, with total excellent effective rate in subjects treated with melatonin [odds ratio = 3.05, 95 % confidence interval (CI) = 1.47, 6.31, P = .003]. Homogeneity was analyzed by fixed effect model (I 2 = 0%). There was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = -0.36, 95% CI = -3.65, 2.92, P = .83). Significant difference was not existed in SaO 2 between the melatonin treatment group and the control group (WMD = 1, 95% CI = -1.21, 3.22, P = .37). In terms of WBC, there was no significant difference between the 2 groups (WMD = -1.07, 95% CI = -2.44, 0.30, P = .13). Conclusions: The meta-analysis showed that melatonin had the beneficial effects for COVID-19 prevention and treatment as an adjunctive agent in combination with basic treatment for the treatment. Abbreviations: CI = confidence interval, COVID-19 = coronavirus pandemic disease 2019, CRP = C-reactive protein, PRM = prolonged-release melatonin, RCT = randomized clinical trials, SaO 2 = arterial oxygen saturation, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, WBC = white blood cells, WMD = weighted mean difference.
Author contributions X.W. finished the data analysis. X.W., G.W., and S.Z. wrote and revised the manuscript. S.Z. conceived and designed the study. Y.C. and S.Z. acquired funding supports and approved the final manuscript as submitted. Formal analysis: Xin-Chen Wang, Shi-Jie Zhang. Investigation: Xin-Chen Wang, Guang-Liang Wu, Shi-Jie Zhang. Project administration: Xin-Chen Wang, Ye-Feng Cai. Resources: Xin-Chen Wang, Guang-Liang Wu, Shi-Jie Zhang. Software: Xin-Chen Wang, Guang-Liang Wu. Supervision: Ye-Feng Cai, Shi-Jie Zhang. Visualization: Ye-Feng Cai. Writing -review & editing: Xin-Chen Wang.
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