Prophylactic treatment protocol against the severity of COVID-19 using melatonin
Dr Nejib Charaa, Pr Mohamed Chahed, Pr Habib Ghedira, Pr Riadh Daghfous
The Corona Virus Disease 2019 pandemic reached more than 150 countries in all continent in two months, after triggering in Wuhan, China in late December 2019. One of the main features of this pandemic is the increased severity of the disease with age and the highest proportion of serious cases among males. Most severe cases were caused by an intensive immune response with massive release of cytokines which induces acute respiratory distress syndrome and multi-visceral failure. Melatonin is the major neuro-hormone secreted by the pineal gland. The synthesis of this hormone shows a circadian pattern. Melatonin secretion gradually decreases with age and becomes clear in people over the age of 60. This deprivation is inversely proportional to the increase in mortality due to COVID-19 with age. Also the level of this hormone seems to be higher in women. It is assumed that melatonin with its immunomodulatory and antiviral actions plays a protective role against the severity of SARS-CoV-2 infection. Following our review, we concluded that this hypothesis was highly plausible and we proposed a prophylactic treatment protocol against the severity of COVID-19 using a melatonin supplementation.
References
Anderson, Reiter, Melatonin: Roles in influenza, Covid-19, and other viral infections, Reviews in Medical Virology,
doi:10.1002/rmv.2109Angeles Bonmati-Carrion, Arguelles-Prieto, Martinez-Madrid, Reiter, Hardeland et al., Protecting the melatonin rhythm through circadian healthy light exposure, International Journal of Molecular Sciences
Ben-Nathan, Maestroni, Lustig, Conti, Protective effects of melatonin in mice infected with encephalitis viruses, Archives of Virology
Borghesi, Radiographic severity index in COVID-19 pneumonia: relationship to age and sex in 783 Italian patients
Carrillo-Vico, Lardone, Nuria, Sánchez, Rodríguez-Rodríguez et al., Melatonin: Buffering the Immune System, International Journal of Molecular Sciences
Carrillo-Vico, Reiter, Lardone, Herrera, Fernández-Montesinos, None
Cascella, Rajnik, Cuomo, Dulebohn, Di, Features, Evaluation and Treatment Coronavirus (COVID-19)
Chen, Huang, Chen, Wang, Yang et al., Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis, International Immunopharmacology
Chen, Wu, Guo, Cao, Huang et al., Clinical and immunological features of severe and moderate coronavirus disease 2019, The Journal of Clinical Investigation
Cipolla, Neto, Gaspar, Amaral, Melatonin as a Hormone: New Physiological and Clinical Insights, Endocrine Reviews
Claustrat, Brun, Chazot, The basic physiology and pathophysiology of melatonin, Sleep Medicine Reviews
Claustrat, Leston, Melatonin: Physiological effects in humans, Neurochirurgie
Daniel, Cardinali, Esquifino, Srinivasan, Pandi-Perumal, Melatonin and the immune system in aging, Neuroimmunomodulation
Dong, Mo, Hu, Qi, Jiang et al., Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China, American Academy of Pediatrics Section
Ennio, Favalli, Ingegnoli, Lucia, Cincinelli et al., COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmunity Reviews
Favero, Franceschetti, Bonomini, Fabrizio Rodella, Rezzani, Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation
Gaspar, Amaral, Cipolla-Neto, A brief review about melatonin, a pineal hormone, Archives of Endocrinology and Metabolism
Gorbalenya, Baker, Baric, De Groot, Drosten et al., and its viruses -a statement of the Coronavirus Study Group
Gu-Jiun Lin, Huang, Chen, Wang, Chang et al., Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases, International Journal of Molecular Sciences
Gunn, Middleton, Davies, Revell, Skene, Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions, Chronobiology International
Hardeland, Aging, Melatonin, and the Pro-and Anti-Inflammatory Networks, International Journal of Molecular Sciences
Hardeland, Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction, TheScien-tificWorldJournal
Hauser, Counotte, Margossian, Konstantinoudis, Low et al., Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: a modelling study in Hubei, China and northern Italy. medRxiv
Hendrick, Crasson, Hagelstein, Bruls, Legros, Approche statistique de l'influence de l'âge et du sexe sur l'excrétion de 6-sulfatoxymélatonine urinaire (a-MT6s) chez l'individu normal
Huang, Cao, Liu, Shi, Wei, Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice, Journal of Pineal Research
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet
Hussin, Rothan, Siddappa, Byrareddy, The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak, Journal of Autoimmunity
Jin, Bai, He, Wu, Liu et al., Gender differences in patients with COVID-19: Focus on severity and mortality
John, Moore, June, Cytokine release syndrome in severe COVID-19
Jordan, Adab, Cheng, Covid-19: risk factors for severe disease and death, BMJ
Karasek, Melatonin, human aging, and age-related diseases, Experimental Gerontology
Lee, Gardner, Porter, Louis, Ahmed et al., Current concepts in the diagnosis and management of cytokine release syndrome, Blood
Lewy, Wehr, Goodwin, Newsome, Markey, Light suppresses melatonin secretion in humans
Li, Geng, Peng, Meng, Lu, Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis
Lippi, Michael, Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19), European Journal of Internal Medicine
Liu, Zhao, Cytokine release syndrome: grading, modeling, and new therapy, Journal of Hematology & Oncology
Livingston, Bucher, Coronavirus Disease 2019 (COVID-19), JAMA
Masson, Mélatonine : aspects physiologiques et pharmacologiques en relation avec le sommeil, intérêt d'une forme galénique à libération prolongée (Circadin R ) dans l'insomnie
Mehta, Mcauley, Brown, Sanchez, Tattersall et al., COVID-19: consider cytokine storm syndromes and immunosuppression, The Lancet
Melatonin, Monograph, None, Alternative Medicine Review: A Journal of Clinical Therapeutic
Miguel, Pozo, The modulatory role of melatonin on immune responsiveness, Current Opinion in Investigational Drugs
Mizumoto, Omori, Nishiura, Age specificity of cases and attack rate of novel coronavirus disease (COVID-19), medRxiv
Obayashi, Saeki, Tone, Iwamoto, Miyata et al., Lower Melatonin Secretion in Older Females: Gender Differences Independent of Light Exposure Profiles, Journal of Epidemiology
Permpoonputtana, Tangweerasing, Mukda, Boontem, Nopparat et al., Long-term administration of melatonin attenuates neuroinflammation in the aged mouse brain, EXCLI Journal
Perras, Kurowski, Dodt, Nocturnal melatonin concentration is correlated with illness severity in patients with septic disease, Intensive Care Medicine
Peter, Andersen, Gögenur, Rosenberg, Reiter, The Safety of Melatonin in Humans, Clinical Drug Investigation
Petrovsky, Harrison, The chronobiology of human cytokine production, International Reviews of Immunology
Peuhkuri, Sihvola, Korpela, Dietary factors and fluctuating levels of melatonin, Food & Nutrition Research
Porcheddu, Serra, Kelvin, Kelvin, Rubino, Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China, The Journal of Infection in Developing Countries
Radogna, Diederich, Ghibelli, Melatonin: A pleiotropic molecule regulating inflammation, Biochemical Pharmacology
Ruan, Yang, Wang, Jiang, Song, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China, Intensive Care Medicine
Shimabukuro-Vornhagen, Gödel, Subklewe, Hans, Stemmler et al., -Baildon. Cytokine release syndrome, Journal for Immunotherapy of Cancer
Silvestri, Rossi, Melatonin: its possible role in the management of viral infections-a brief review, Italian Journal of Pediatrics
Siordia, Epidemiology and clinical features of COVID-19: A review of current literature, Journal of Clinical Virology
Srinivasan, Maestroni, Cardinali, Esquifino, Sr Pandi Perumal et al., Melatonin, immune function and aging, Immunity & Ageing
Srinivasan, Mohamed, Kato, Melatonin in Bacterial and Viral Infections with Focus on Sepsis: A Review. Recent patents on endocrine, metabolic & immune drug discovery
Stephen, Shiu, Reiter, Tan, Shiu et al., Urgent search for safe and effective treatments of severe acute respiratory syndrome: is melatonin a promising candidate drug?, Journal of Pineal Research,
doi:10.1034/j.1600-079X.2003.00068.xSun, Chen, Viboud, Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a populationlevel observational study, The Lancet Digital Health
Sundberg, Rasmusson, Ramklint, Just, Ekselius et al., Daytime melatonin levels in saliva are associated with inflammatory markers and anxiety disorders, Psychoneuroendocrinology
Szczepanik, Melatonin and its influence on immune system, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
Tezer, Bedir, Novel coronavirus disease (COVID-19) in children, Turkish Journal of Medical Sciences
Touitou, Arendt, Pévet, Melatonin and the Pineal Gland, from Basic Science to Clinical Application
Touitou, Human aging and melatonin. Clinical relevance, Experimental Gerontology
Touitou, Mélatonine : de la physiologie à la pathologie, EMC -Endocrinologie -Nutrition
Wang, Hu, Hu, Zhu, Liu et al., Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China, JAMA
Wenham, Smith, Morgan, COVID-19: the gendered impacts of the outbreak, The Lancet
Who Director, General's remarks at the media briefing on 2019-nCoV on 11
Wu, Chou, Chao, Chang, Lin et al., Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats, Acta Pharmacologica Sinica
Wu, Peng, Liao, Pao, Huang et al., Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production, Respiratory Research
Zhang, Wu, Li, Zhao, Wang, The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality, International Journal of Antimicrobial Agents
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, The Lancet
DOI record:
{
"DOI": "10.2139/ssrn.3601861",
"ISSN": [
"1556-5068"
],
"URL": "http://dx.doi.org/10.2139/ssrn.3601861",
"author": [
{
"affiliation": [],
"family": "Charaa",
"given": "Nejib",
"sequence": "first"
},
{
"affiliation": [],
"family": "Chahed",
"given": "Mohamed",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ghedira",
"given": "Habib",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Daghfous",
"given": "Riadh",
"sequence": "additional"
}
],
"container-title": "SSRN Electronic Journal",
"container-title-short": "SSRN Journal",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2020,
5,
20
]
],
"date-time": "2020-05-20T21:08:42Z",
"timestamp": 1590008922000
},
"deposited": {
"date-parts": [
[
2020,
5,
20
]
],
"date-time": "2020-05-20T21:09:18Z",
"timestamp": 1590008958000
},
"indexed": {
"date-parts": [
[
2023,
8,
23
]
],
"date-time": "2023-08-23T21:27:22Z",
"timestamp": 1692826042606
},
"is-referenced-by-count": 2,
"issued": {
"date-parts": [
[
2020
]
]
},
"language": "en",
"member": "78",
"original-title": [],
"prefix": "10.2139",
"published": {
"date-parts": [
[
2020
]
]
},
"published-other": {
"date-parts": [
[
2020
]
]
},
"publisher": "Elsevier BV",
"reference-count": 0,
"references-count": 0,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.ssrn.com/abstract=3601861"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Prophylactic Treatment Protocol against the Severity of COVID-19 Using Melatonin",
"type": "journal-article"
}
