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0 0.5 1 1.5 2+ Mortality 94% Improvement Relative Risk Ventilation 89% Hospitalization time 34% no CI Melatonin  Castillo et al.  LATE TREATMENT Is late treatment with melatonin beneficial for COVID-19? Retrospective 41 patients in Philippines (March - April 2020) Lower mortality (p=0.085) and ventilation (p=0.32), not sig. c19early.org Castillo et al., Melatonin Research, Jun 2020 Favors melatonin Favors control

Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series

Castillo et al., Melatonin Research, doi:10.32794/mr11250063
Jun 2020  
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Melatonin for COVID-19
10th treatment shown to reduce risk in December 2020
 
*, now known with p = 0.0000002 from 18 studies.
Lower risk for mortality, ventilation, and recovery.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments. c19early.org
Report on the use of high-dose melatonin in 10 pneumonia patients, showing clinical stabilization and/or improvement for all patients within 4-5 days. All patients survived, including 3 with moderately severe ARDS and one with mild ARDS. None required mechanical ventilation.
This study is excluded in meta analysis: unadjusted results with no group details.
risk of death, 93.5% lower, RR 0.06, p = 0.08, treatment 0 of 7 (0.0%), control 12 of 34 (35.3%), NNT 2.8, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), COVID+.
risk of mechanical ventilation, 89.4% lower, RR 0.11, p = 0.32, treatment 0 of 7 (0.0%), control 7 of 34 (20.6%), NNT 4.9, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), COVID+.
hospitalization time, 33.8% lower, relative time 0.66, treatment 7, control 34, COVID+.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Castillo et al., 15 Jun 2020, retrospective, Philippines, peer-reviewed, 10 authors, study period 5 March, 2020 - 4 April, 2020.
This PaperMelatoninAll
Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series
Rafael Ricafranca Castillo, Gino Rei A Quizon, Mario Joselito M Juco, Arthur Dessi E Roman, Donnah G De Leon, Felix Eduardo R Punzalan, Rafael Bien L Guingon, Dante D Morales, Dun-Xian Tan, Russe J Reiter
Melatonin Research, doi:10.32794/mr11250063
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 Research (Melatonin Res.
AUTHORSHIP Rafael Castillo: Conception and design, analysis and interpretation of data, drafting the manuscript and revising it critically for important intellectual content, gave final approval of version to be published; Gino Rei Quizon: Acquisition of data, analysis and interpretation of data, revision of manuscript, gave final approval of version to be published; Felix Eduardo Punzalan: Analysis and interpretation of data, revision of manuscript, gave final approval of version to be published; Dante Morales: Conception and design, or analysis and interpretation of data, gave final approval of version to be published; Mario Joselito Juco: Acquisition of data, analysis and interpretation of data; Arthur Dessi Roman: Acquisition of data, analysis and interpretation of data; Donnah de Leon: Acquisition of data, analysis and interpretation of data; Rafael Bien Guingon: Acquisition of data, analysis and interpretation of data, gave final approval of version to be published. Dun Xian Tan, identification and interpretation of data; Russel J. Reiter, identification and interpretation of data, suggestions for information to be included in the paper and minor editing of the manuscript. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CONFLICT OF INTEREST Rafael R. Castillo: member of speakers bureau and advisory board of Servier,..
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Late treatment
is less effective
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