Abstract: Trial iew ed The effect of melatonin as an adjuvant therapy on COVID-19: A Randomized Clinical Najmeh Davoodian1,2, *, Farnoosh Sharifimood1, Davoud Salarbashi2,3,**, Sepideh Elyasi4,**, Amir Baniasad5,**, Farhang Soltani Bejestani6 1Department of Internal Medicine, Clinical Research Development Unit, Bohlool Hospital, Gonabad University of Medical Sciences, Gonabad, Iran. Diseases Research Centre, Gonabad University of Medical Sciences, Gonabad, Iran. 3Department ev 2Infectious of Nutrition and food science, School of Medicine, Gonabad University of Medical 4Department er r Sciences, Gonabad, Iran. of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. of Internal Medicine, School of Medicine, Kerman University of Medical Sciences, pe 5Department Kerman, Iran. 6Department of Rheumatology, Faculty of Medicine, Gonabad University of Medical Sciences, ot Gonabad, Iran tn *Corresponding to: Department of Internal Medicine, Gonabad University of Medical Sciences, Gonabad, Iran. Email: najmeh.davoudian@gmail.com Pr ep rin **Co-corresponding author This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3878090 iew ed Summary Background: Melatonin is secreted by the pineal gland and has antioxidant and anti-inflammatory properties. So, it is proposed to be effective in the management of Coronavirus disease 2019 (COVID-19). This study aimed to evaluate the effect of melatonin as adjunctive therapy for the treatment of hospitalized patients with mild to moderate COVID-19. ev Methods: In this double-blind randomized placebo controlled clinical trial, 81 mild to moderate hospitalized COVID-19 patients with inclusion criteria were randomly divided to treatment (n=42) group to receive melatonin tablet 3 mg, three times daily for 2 weeks or placebo (n=39) group. Patients’ symptoms and laboratory data were er r assessed at baseline and during the follow-up period and compared between two groups. Findings: After two weeks of follow-up, the oxygen saturation and the respiratory rate significantly improved in the melatonin group. Moreover, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), Ferritin, and D-Dimer levels significantly decreased in the melatonin group, but there was a considerable increase in the placebo group. Between-group comparison showed a pe significant difference between melatonin and placebo groups. Interpretation: the results of this randomized, double-blind, placebo-controlled trial indicated the high efficacy and safety of melatonin as an adjuvant therapy in patients with mild to moderate COVID-19 disease. Further study ot with large sample size and on other populations like severe COVID-19 is recommended. Funding: This article was sponsored by the Research Council of Gonabad University of Medical Sciences Pr ep rin tn (Gonabad, Iran) This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3878090 iew ed