Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial

Abstract

Background: Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19).

Aim of the study: To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19.

Methods: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020-June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks.

Results: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups.

Conclusions: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Keywords: Adjunctive therapy; COVID-19; Clinical trial; Melatonin.

Figure 1

CONSORT flow diagram of patient enrolled through the clinical trial.

Figure 2

Chest CT images of the representative hospitalized patients with COVID-19. A. chest CT scans of a 39 year old male patient with COVID-19 pneumonia who received melatonin as an adjuvant treatment; B. chest CT scans of a 48 year-old male patient with COVID-19 pneumonia who only received standard of care. CT was performed in three stages, including I) the day of admission before treatment onset, II) 5 d after treatment and, III) 12 d after treatment. COVID‐19, coronavirus disease 2019; CT, computed tomography. AI: CT image show multifocal ground-glass opacities and consolidation lesions. AII: CT image show bilateral multiple ground-glass opacity. AIII: CT image show very faint and smaller ground-glass opacities in both lungs. BI: CT image show consolidation lesions and ground-glass opacities with Interlobular septal thickening called crazy paving pattern. BII: CT image show bilateral ground-glass opacities and atelectasis in the segment of the left upper lobe. BIII: CT image show bilateral ground-glass opacities.