Lan · Journal of medical virology 2022 · systematic review and meta-analysis of randomized controlled trials · n=3 studies

Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Cited 43 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 35032042 · doi:10.1002/jmv.27595 · record verified 2026-08-29

What was done

A systematic review and meta-analysis of randomized controlled trials (RCTs) searched PubMed, Web of Science, Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov up to September 11, 2021. Eligible studies compared melatonin with placebo for clinical efficacy in COVID-19 patients. Melatonin dosing was 3 mg three times daily in one trial and 3–6 mg daily at bedtime in two trials; durations were 7 or 14 days. The primary outcome was clinical recovery rate.

What was found

Three RCTs were included. Clinical recovery rates were 94.2% (81/86) with melatonin versus 82.4% (70/85) with control (OR: 3.67; 95% CI: 1.21–11.12; I² = 0%, p = 0.02). ICU admission risk was numerically lower but not statistically significant (8.3% [6/72] vs. 17.6% [12/68]; OR: 0.45; 95% CI: 0.16–1.25; I² = 0%, p = 0.13), as was mortality (1.4% [1/72] vs. 4.4% [3/68]; OR: 0.32; 95% CI: 0.03–3.18; I² = 0%, p = 0.33).

Why it matters

This review provides early meta-analytic evidence that adjuvant melatonin may accelerate clinical recovery in COVID-19, though findings require confirmation in larger trials.

Limits

The total sample size is very small (3 RCTs, 171 total patients for the primary outcome), resulting in wide confidence intervals. Melatonin dosing and treatment duration varied across the included trials. The analysis was underpowered to detect differences in ICU admission or mortality.

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