Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial
Ali Ameri, Masoomeh Frouz Asadi, Ava Ziaei, Majid Vatankhah, Omid Safa, Manoochehr Kamali, Mohammad Fathalipour, Masoumeh Mahmoodi, Soheil Hassanipour
Inflammopharmacology, doi:10.1007/s10787-022-01096-7
Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27-18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34-4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13-17) in the melatonin group and 21 days (14-24) in the control group (OR; 5.00, 95% CI, 0.15-9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9-13) in the melatonin group and 16 days (10-19) in the control group (OR; 3.92, 95% CI, 1.69-6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s10787-022-01096-7. Author contributions AA, AZ, and MF: conceptualization, methodology, software. MF, MM, and SH: data curation, writing-original draft preparation. MF, MV, OS, and MK: visualization, investigation. AAi: supervision. SH: software, validation. MF: writing-reviewing and editing.
Declarations Conflict of interest None of the authors have a conflict of interest to disclose. Ethical approval and consent to participate Ethics approval was obtained from the ethics committee of Hormozgan University of Medical Sciences (IR.HUMS.REC.1399.526). The study was also undertaken in accordance with the guidelines of the Declaration of Helsinki and the principles of the International Conference on Harmonization Good Clinical Practice.
Consent for publication A written informed consent was obtained from all patients. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
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