Abstract: May 4, 2020 Review iew ed Prophylactic treatment protocol against the severity of COVID-19 using melatonin Dr Nejib CHARAA1 *, Pr Mohamed CHAHED2 , Pr Habib GHEDIRA 3 , Pr Riadh DAGHFOUS4 er r ev Abstract The Corona Virus Disease 2019 (COVID-19) 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. Keywords COVID-19 — SARS-CoV-2 — Coronavirus — Melatonin — Prophylaxis — Treatment 1 Preventive Health Director. Regional Health Directorate of Kebili, Tunisia of Epidemiology and Public Health, Faculty of Medicine of Tunis, Tunis-El Manar University, Tunis, Tunisia 3 Head of Pulmonary Diseases Dpt I - A. Mami Chest Diseases Hospital, Ariana 2080, Tunisia 4 National Center of Pharmacovigilance General Director. University of Tunis El Manar Department of Basic Sciences B, Tunisia. *Corresponding author: n.charaa@gmail.com Contents