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Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status

Centre for Addiction and Mental Health, Molecular Brain Sciences, Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
Somnogen Canada Inc., Toronto, ON M6H 1C5, Canada
Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai 600077, India
Primary Care Mental Health Physician, Bathurst St., Toronto, ON M3H 3S3, Canada
Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires 1007, Argentina
Author to whom correspondence should be addressed.
Academic Editors: Maurizio Battino and Amal K. Mitra
Diseases 2021, 9(3), 64;
Received: 21 August 2021 / Revised: 14 September 2021 / Accepted: 14 September 2021 / Published: 20 September 2021
This brief review was written to provide a perspective on the flurry of reports suggesting that melatonin can be an important add-on therapy for COVID-19. Despite the passage of more than 60 years since its discovery and much evidence representing the contrary, there has been great reluctance to conceive melatonin as anything other than a hormone. Many other body chemicals are known to have multiple roles. Melatonin was first shown to be a hormone derived from the pineal gland, to be actively synthesized there only at night, and to act on targets directly or via the G-protein-coupled receptors (GPCRs) superfamily. It is of note that over 40 years ago, it was also established that melatonin is present, synthesized locally, and acts within the gastrointestinal tract. A wider distribution was then found, including the retina and multiple body tissues. In addition, melatonin is now known to have non-hormonal actions, acting as a free radical scavenger, an antioxidant, and as modulating immunity, dampening down innate tissue responses to invaders while boosting the production of antibodies against them. These actions make it a potentially excellent weapon against infection by the SARS-CoV-2 virus. Early published results support that thesis. Recently, a randomized controlled study reported that low doses of melatonin significantly improved symptoms in hospitalized COVID-19 patients, leading to more rapid discharge with no side effects, while significantly decreasing levels of CRP, proinflammatory cytokines, and modulating dysregulated genes governing cellular and humoral immunity. It is now critical that these trials be repeated, with dose-response studies conducted and safety proven. Numerous randomized controlled trials are ongoing, which should complete those objectives while also allowing for a more thorough evaluation of the mechanisms of action and possible applications to other severe diseases. View Full-Text
Keywords: melatonin; COVID-19; RCT; immunity; cytokines; mitochondria; antioxidant melatonin; COVID-19; RCT; immunity; cytokines; mitochondria; antioxidant
MDPI and ACS Style

Brown, G.M.; Pandi-Perumal, S.R.; Pupko, H.; Kennedy, J.L.; Cardinali, D.P. Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status. Diseases 2021, 9, 64.

AMA Style

Brown GM, Pandi-Perumal SR, Pupko H, Kennedy JL, Cardinali DP. Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status. Diseases. 2021; 9(3):64.

Chicago/Turabian Style

Brown, Gregory M., Seithikurippu R. Pandi-Perumal, Harold Pupko, James L. Kennedy, and Daniel P. Cardinali. 2021. "Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status" Diseases 9, no. 3: 64.

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