Abstract: Melatonin Research (Melatonin Res.) http://www.melatonin-research.net Research Article Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series Rafael R. Castillo*1,2,4, Gino Rei A. Quizon^ 1, Mario Joselito M. Juco1, Arthur Dessi E. Roman1, Donnah G. de Leon1, Felix Eduardo R. Punzalan1,3, Rafael Bien L. Guingon1, Dante D. Morales1,5, Dun-Xian Tan6, Russel J. Reiter7; on behalf of the MAC-19 PRO Study Group 1 Department of Internal Medicine, Manila Doctors Hospital, Manila, Philippines Cardiovascular Medicine, Adventist University of the Philippines, College of Medicine, Silang, Philippines 3 University of the Philippines, College of Medicine; Manila, Philippines 4 CardioMetabolic Research Unit (CaMeRU), FAME Leaders Academy, Makati, Philippines 5 Section of Cardiology, Makati Medical Center, Makati, Philippines 6 S.T. Bio-Life; San Antonio, Texas, USA 7 Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, Texas, USA ^ Joint first author *Correspondence: rafael.castillo@fame.ph, medicalfiles.inquirer@gmail.com, Tel: +63 917 886 8409 2 Running Title: Adjuvant melatonin treatment in COVID19 pneumonia Received: April 30, 2020; Accepted: June 3, 2020 ABSTRACT Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19. We aimed to describe the observable clinical outcomes and tolerability of high-dose melatonin (hdM) given as adjuvant therapy in patients admitted with COVID19 pneumonia. We conducted a retrospective descriptive case series of patients who: 1) were admitted to the Manila Doctors Hospital in Manila, Philippines, between March 5, 2020 and April 4, 2020; 2) presented with history of typical symptoms (fever, cough, sore throat, loss of smell and/or taste, myalgia, fatigue); 3) had admitting impression of atypical pneumonia; 4) had history and chest imaging findings highly suggestive of COVID19 pneumonia, and, 5) were given hdM as adjuvant therapy, in addition to standard and/or empirical therapy. One patient admitted to another hospital, who one of the authors helped co-manage, was included. He was the lone patient given hdM in that hospital during the treatment period. Main outcomes described were: time to clinical improvement, duration of hospital stay from hdM initiation, need for mechanical ventilation (MV) prior to cardiopulmonary resuscitation, and final outcome (death or recovery/discharge). Of 10 patients given hdM at doses of 36-72mg/day per os (p.o.) in 4 divided doses as adjuvant therapy, 7 were confirmed COVID19 positive (+) by reverse transcription polymerase chain reaction (RT-PCR) and 3 tested negative (-), which was deemed to be false (-) considering the patients’ typical history, symptomatology, chest imaging Melatonin Res. 2020, Vol 3 (3) 297-310; doi: 10.32794/mr11250063 297 Melatonin Research (Melatonin Res.) http://www.melatonin-research.net findings and elevated bio-inflammatory parameters. In all 10 patients given hdM, clinical stabilization and/or improvement was noted within 4-5 days after initiation of hdM. All hdM patients,..