Protective Effect of Melatonin Administration against SARS-CoV-2 Infection: A Systematic Review.

INTRODUCTION: according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and healthcare professionals: global immunization (which is still far from being achieved) and the availability of drugs capable of preventing its consequences in the infected patient. In this sense, the role that melatonin can play is has been assessed in the recent literature. Justification and Objectives: the serious health, social and economic consequences of COVID-19 have forced an urgent search for preventive methods, such as vaccines, among others, and therapeutic methods that could be alternatives to the drugs currently used. In this sense, it must be accepted that one of the most recommended has been the administration of melatonin. The present study proposes to carry out a systematic review of its possible role in the treatment and/or prevention of COVID-19. Material and methods: a systematic review of the literature related to the prevention of COVID-19 through the administration of melatonin was carried out, following the sequence proposed by the Prisma Declaration regarding the identification and selection of documents, using the specialized health databases Trip Medical Database, Cochrane Library, PubMed, Medline Plus, BVS, Cuiden and generic databases such as Dialnet, Web of Science and Google Scholar for their retrieval. Appropriate inclusion and exclusion criteria are described for the articles assessed. The main limitation of the study has been the scarcity of works and the lack of defining a specific protocol in terms of dosage and administration schedule. Results: once the selection process was completed, and after an in-depth critical analysis, 197 papers were selected, and 40 of them were finally used. The most relevant results were: (1) melatonin prevents SARS-CoV-2 infection, (2) although much remains to be clarified, at high doses, it seems to have a coadjuvant therapeutic effect in the treatment of SARS-CoV-2 infection and (3) melatonin is effective against SARS-CoV-2 infection. Discussion: until group immunization is achieved in the population, it seems clear that we must continue to treat patients with SARS-CoV-2 infection, and, in the absence of a specific and effective antiviral therapy, it is advisable to continue researching and providing drugs that demonstrate validity based on the scientific evidence. In this regard, we believe that the available studies recommend the administration of melatonin for its anti-inflammatory, antioxidant, immunomodulatory, sleep-inducing, CD147, Mpro, p65 and MMP9 protein suppressing, nephrotoxicity-reducing and highly effective and safe effects. Conclusions: (1) melatonin has anti-inflammatory, antioxidant, immunomodulatory, and Mpro and MMP9 protein-inhibitory activity. (2) It has been shown to have a wide margin of safety. (3) The contributions reviewed make it an effective therapeutic alternative in the treatment of SARS-CoV-2 infection. (4) Further clinical trials are recommended to clearly define the administration protocol.

Clinical Considerations Derived From the Administration of Melatonin to Children With Sleep Disorders.

BACKGROUND AND OBJECTIVES: Despite the numerous investigations carried out in relation to melatonin, there is a lack of knowledge about the specific melatonin secretion patterns in the diverse primary sleep disturbances. The objective of this study was to analyze the plasma melatonin concentrations in children with primary sleep disorders and the effects of melatonin therapy on their serum levels and their actigraphic sleep parameters. METHODS: Fourteen participants (nine girls; seven to 14 years old) diagnosed with diverse primary sleep disorders were recruited. Four different melatonin secretion patterns were identified: low plasma melatonin levels, absence of a circadian rhythm, advanced acrophase, and delayed acrophase. A placebo (one week) was administered followed by three months of melatonin therapy (3 mg/night). Urinary 6-sulfatoxymelatonin levels, 24-hour plasma melatonin concentrations, and a seven-day actigraphic record were collected after both treatments. RESULTS: After melatonin therapy, a significant increase (P < 0.001) of urinary 6-sulfatoxymelatonin excretion with a clear circadian variation was observed. Plasma melatonin concentrations were also significantly higher with a recovery in the circadian rhythm. Actual sleep time was significantly longer, with a substantial reduction in the sleep onset latency and night awakenings. No severe side effects were reported. CONCLUSIONS: The main clinical implication of this study is to demonstrate the efficacy of melatonin in three main circumstances: an insufficient hormone production, a disturbed circadian rhythm, and an advanced or delayed acrophase. As ongoing work, we are exploring the effect of different doses of melatonin on the regulation of its concentrations and of its secretion rhythm.

Analysis of Different Melatonin Secretion Patterns in Children With Sleep Disorders: Melatonin Secretion Patterns in Children.

The objective of this study was to analyze circadian patterns of urinary 6-sulphatoxymelatonin (aMT6s) excretion in children with primary sleep disorders in comparison with healthy controls. A total of 124 control children and 124 patients (aged 4-14 years) diagnosed with diverse primary sleep disorders were recruited. aMT6s concentrations were measured in diurnal and nocturnal urine, as well as in 24-hour urine. aMT6s levels were significantly higher and showed significantly more evident circadian variations in the control group ( P < .001). Four different melatonin (aMT) production and excretion patterns were distinguished in the group with sleep disorders: (1) standard aMT production pattern, (2) low aMT production pattern, (3) aMT production pattern with absence of circadian variation, and (4) aMT hyperproduction pattern. This study highlights the importance of analyzing specific alterations of aMT secretion in each sleep disorder and provides evidences to explain why not all children with sleep disturbances do respond to aMT treatment.