The role of melatonin as an adjuvant in the treatment of COVID-19: A systematic review.

Introduction: Since November 2019, the world has been grappling with the rapid spread of the Coronavirus disease 2019 (COVID-19). In response to this major health crisis, the first vaccination rollout was launched in December 2020. However, even fully vaccinated individuals are not completely immune to infection, albeit with less severe symptoms. Melatonin is known as an anti-oxidant, anti-inflammatory, and immunomodulatory agent whose anti-viral properties, cost-effectiveness, and relatively few side effects make it a potential adjuvant in the treatment of COVID-19. This systematic review aims to summarize the clinical studies on the effects of melatonin on COVID-19 patients. Methods: The search of articles was carried out in the Web of Science, PubMed/MEDLINE, Cochrane library, and Scopus databases up to January 2022. Results: Ten articles were included in our study. It seems melatonin can decrease inflammatory markers, inflammatory cytokines, and the expression of some genes, including the signal transducer and activator of transcription (STAT)4, STAT6, T-box expressed in T cell (T-bet), GATA binding protein 3 (GATA3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 (CASP1). In addition, melatonin appears to alleviate some clinical signs and symptoms and accelerate recovery. The use of melatonin in severe cases reduces thrombosis, sepsis, and mortality rate. Conclusion: This systematic review highlights the probable role of melatonin as a potential adjuvant in the treatment of COVID-19 after about two weeks of consumption. However, further high-quality randomized clinical trials are required.