Table 4. Clinical Studies Involving Melatonin in the Treatment of COVID-19.

Trial details	Dose	Outcomes	Comments/level of evidence
Randomized single blind trial. Treatment: n = 14. Control: n = 17. Age: 25 - 65 years. Hospitalized mild moderate COVID-19 [145]	6 mg melatonin at bedtime for 14 days	Improved declined CRP in treatment group. Percentage of recovery (based on symptoms) in patients who took melatonin was higher than that of patients in the control group (85.7% vs. 47.1%)	Corticosteroids given. Level of evidence 2
Double blind randomized controlled trial. Treatment: n = 24. Control: n = 20. Age: 36 - 64 years. Mild to moderate COVID-19 [146]	3 mg melatonin three times a day for 14 days	Faster time to symptom resolution, faster time to discharge. Improvement in CRP	Unclear if standard of care included corticosteroids. Level of evidence 2
Randomized open label study. Treatment: n = 48. Control: n = 48. Age: 36 - 69 years. Mild to moderate COVID-19 [147]	3 mg at bedtime for 7 days	Improvement in oxygenation	Higher usage of methylprednisolone in control group. Level of evidence 2
Retrospective study. Patients: n = 791. Mean age: 56 years. Patients received melatonin: n = 112 [148]	112 patients received melatonin	Improved survival in those patients who received melatonin	Study adjusted for comorbidities and therapy including corticosteroids. Level of evidence 3

Based on level 5 evidence (cited in text) and current studies, we recommend the use of melatonin as adjunctive therapy in patients with COVID-19. CRP: C-reactive protein.