Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: Systematic review and meta-analysis.

BACKGROUND: Melatonin might be beneficial to coronavirus disease 2019 (COVID-19) patients in terms of both prevention and treatment. We investigated how melatonin affected various clinical and laboratory results in COVID-19 patients.

METHODS: PubMed, Scopus, Cochrane Library and Web of Science databases were utilized for searching eligible articles fulfilling our inclusion criteria up to December 2022. We used random effect model in case of significant heterogeneity; in other cases, a fixed model was applied. RevMan was used for meta-analysis.

RESULTS: We included 11 studies in our review. Clinical improvement rate was found to be statistically significantly higher in patients taking melatonin than in the control group (OR: 5.09; 95% CI: 2.60-9.96, p ​< ​0.001). Patients receiving melatonin showed a non-significant difference in mortality rate compared to the control group (OR: 0.37; 95% CI: 0.07-1.81, p ​= ​0.22). However, in the randomized controlled trials subgroup, melatonin-treated patients showed significantly lower mortality than did the controls (OR: 0.17; 95% CI: 0.08-0.38, p ​< ​0.001). CRP level was statistically significantly lower due to melatonin treatment (weighted mean difference [WMD] ​= ​-9.85; 95% CI: -18.54 to -1.16, p ​= ​0.03). Length of hospital stay was statistically significantly shorter in patients taking melatonin compared to controls (WMD ​= ​-4.05; 95% CI: -5.39 to -2.7, p ​< ​0.001).

CONCLUSION: Melatonin was found to have substantial effects on COVID-19 patients when used as adjuvant therapy, enhancing clinical improvement and decreasing time to recovery with a shorter length of hospital stay and a shorter duration of mechanical ventilation.