Abstract: MINI REVIEW published: 15 May 2020 doi: 10.3389/fmed.2020.00226 Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19 Russel J. Reiter 1*, Pedro Abreu-Gonzalez 2 , Paul E. Marik 3 and Alberto Dominguez-Rodriguez 4,5,6* 1 Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX, United States, 2 Department of Physiology, Faculty of Medicine, University of La Laguna, San Cristóbal de La Laguna, Spain, 3 Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA, United States, 4 Department of Cardiology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain, 5 Facultad de Ciencias de la Salud, Universidad Europea de Canarias, Santa Cruz de Tenerife, Spain, 6 CIBER de enfermedades CardioVasculares (CIBERCV), Madrid, Spain Edited by: Zisis Kozlakidis, International Agency for Research on Cancer (IARC), France Reviewed by: Irene Crespo, University of León, Spain Abdul Alim Al-Bari, University of Rajshahi, Bangladesh Javier González-Gallego, University of León, Spain *Correspondence: Russel J. Reiter reiter@uthscsa.edu Alberto Dominguez-Rodriguez adrvdg@hotmail.com Specialty section: This article was submitted to Infectious Diseases – Surveillance, Prevention and Treatment, a section of the journal Frontiers in Medicine Received: 06 April 2020 Accepted: 04 May 2020 Published: 15 May 2020 Citation: Reiter RJ, Abreu-Gonzalez P, Marik PE and Dominguez-Rodriguez A (2020) Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19. Front. Med. 7:226. doi: 10.3389/fmed.2020.00226 Frontiers in Medicine | www.frontiersin.org The coronavirus, COVID-19, has infected hundreds of thousands and killed tens of thousands of individuals worldwide. This highly infectious condition continues to ravage the world population and has yet to reach it peak infective rate in some countries. Many conventional drugs including hydroxychloroquine/chloroquine, lopinavir, remdesivir, etc., have been repurposed as treatments for this often deadly disease, but there is no specifically-designed effective drug available; also, the drugs mentioned have significant side effects and their efficacy is unknown. New drugs and vaccines are being designed as COVID-19 treatment, but their development and testing will require months to years. Time is not a luxury that this crisis has. Thus, there is a serious unmet need for the identification of currently-available and safe molecules which can be used to slow or treat COVID-19 disease. Here, we suggest melatonin be given consideration for prophylactic use or treatment alone or in combination with other drugs. Melatonin’s multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) make it a reasonable choice for use. Melatonin is readily available, can be easily synthesized in large quantities, is inexpensive, has a very high safety profile and can be easily self-administered. Melatonin is endogenously-produced molecule in small amounts with its production diminishing with increased age. Under the current critical conditions, large doses of melatonin alone or in combination with currently-recommended drugs, e.g., hydroxychloroquine/chloroquine, to resist COVID-19 infection would seem judicious. Keywords: melatonin, COVID-19, SARS-CoV-2, treatment-drug, prevention & control