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Faridzadeh A, Tabashiri A, Miri HH, Mahmoudi M. The role of melatonin as an adjuvant in the treatment of COVID-19: A systematic review. Heliyon. 2022;8(10):e10906. doi:10.1016/j.heliyon.2022.e10906
This systematic review, carried out under the PRISMA guidelines, summarizes the findings of 10 studies on the use of melatonin in COVID-19 patients. Melatonin has been explored in clinical studies due to its anti-inflammatory, antioxidant, and immunoregulatory properties. In addition to being a potent ROS scavenger, melatonin is also a potent myeloperoxidase (MPO) inhibitor. Myeloperoxidase is produced with the over-activation of neutrophils, known as a “cytokine storm”.
Our comments/takeaway from the article:
This review of studies, including humans, is relevant as the literature is still emerging on the use of melatonin in COVID-19 patients, with a number of studies or trials focused on a molecular base or animal models. As it is well established that melatonin is a powerful antioxidant, free radical scavenger, and anti-inflammatory agent, it is plausible that the use of melatonin may help in the recovery of COVID-19 patients. As the clinical use and dose of melatonin have not yet been established for COVID-19, it is best to work with a healthcare provider to determine if this is a viable option in the management of COVID-19.
PICO framework included:
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Population- Adults over 18 years of age with COVID-19 (mild to severe symptoms), diagnosed by CT or PCR testing (n=665)
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Intervention- Melatonin
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Comparison- Comorbidities, gender, severity, melatonin dosage, and duration
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Outcomes – changes in inflammatory markers, clinical signs, and symptoms (from baseline to last available follow-up)
Studies included:
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Observational retrospective cohorts (2)
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Randomized controlled trials (5)
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Clinical trials* (3)
*High risk of bias was noted for the clinical trials.
Melatonin dosing:
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2-10 mg/day
Results:
Melatonin decreased inflammatory markers, including:
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c-reactive protein (CRP)
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erythrocyte sedimentation rate (ESR)
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lactate dehydrogenase (LDH)
Melatonin decreased inflammatory cytokines, including:
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interleukin (IL)-4
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interferon- g (IFN-g)
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IL-6
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IL-1B
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Tumor necrosis factor-a (TNF-a)
A decrease was noted after 14 days of consumption.
Melatonin decreased gene expression, including:
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Signal transducer and activator of transcription (STAT) 4
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STAT-6
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T-box expressed in T cell (T-bet)
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GATA binding protein 3 (GATA3)
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Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)
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Caspase 1 (CASP1)
These immune cell regulatory genes are upregulated in COVID-19, leading to an excessive immune response and cytokine storm.
Melatonin improved clinical signs and symptoms, including:
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Sleep
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Cough
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Fatigue
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Dyspnea
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Decreased intubation period
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Quicker return to baseline health
Authors (of article) conclusion:
The authors conclude that there is a probable role of melatonin as a potential adjuvant in the treatment of COVID-19, when taken for 2 weeks, to reduce recovery time, though further studies are warranted, including larger RCTs.
Article reviewed by Kim Ross, DCN
Content reviewed by Deanna Minich, PhD
October 28, 2022