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Summary of COVID-19 melatonin studies

Studies   Meta Analysis   Hide extended summaries

226 patient melatonin ICU RCT: 29% lower mortality (p<0.0001), 28% lower ventilation (p=0.003), 25% improved recovery (p=0.001), and 29% shorter hospitalization (p=0.03).
RCT 226 ICU patients in Iran, showing lower mortality with melatonin treatment.

Nov 2022, Inflammopharmacology, https://link.springer.com/10.1007/s10787-022-01096-7, https://c19p.org/ameri

158 patient melatonin late treatment RCT: 93% lower mortality (p=0.0004).
RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment.

Oct 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221007980, https://c19p.org/hasan

44 patient melatonin late treatment RCT: 81% lower ICU admission (p=0.2) and 49% faster recovery (p=0.004).
RCT 44 hospitalized patients in Iran, 24 treated with melatonin, showing faster recovery with treatment. There was no mortality.

Jun 2021, Archives of Medical Research, https://www.sciencedirect.com/science/article/pii/S0188440921001417, https://c19p.org/farnoosh

11,672 patient melatonin prophylaxis study: 58% fewer cases (p<0.0001).
Retrospective 11,672 patients tested for COVID-19 with 818 testing positive, showing significantly lower risk with melatonin use.

Jun 2020, Chest, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286244/, https://c19p.org/jehi

80 patient melatonin late treatment study: 50% lower mortality (p=0.48), 50% lower ICU admission (p=0.48), 9% shorter hospitalization (p=0.05), and 58% lower need for oxygen therapy (p<0.0001).
Retrospective 40 hospitalized patients in Italy treated with melatonin and 40 control patients, showing improved sleep, reduced delirium, shorter hospitalization and oxygen times, and reduced ICU admission and mortality (not statistically significant).

Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/24/5857, https://c19p.org/bologna

948 patient melatonin ICU study: 87% lower mortality (p<0.0001).
Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.15.20213546v1, https://c19p.org/ramlall

26,779 patient melatonin prophylaxis PSM study: 21% fewer cases (p=0.01).
PSM observational study with a database of 26,779 patients in the USA, showing significantly lower risk of PCR+ with melatonin usage.

Nov 2020, PLOS Biology, https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000970, https://c19p.org/zhou2

96 patient melatonin late treatment RCT: 67% lower mortality (p=0.62) and 40% lower ICU admission (p=0.41).
RCT 96 hospitalized patients in Iran, 48 treated with melatonin, showing improved sleep quality and SpO2 with treatment. 3mg oral melatonin daily. Authors recommend studies with a higher dose. IRCT20200411047030N1.

Aug 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27312, https://c19p.org/mousavi

31 patient melatonin early treatment RCT: 73% improved recovery (p=0.06).
Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment.

May 2021, Iranian J. Allergy, Asthma and Immunology, https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3086, https://c19p.org/alizadeh

66 patient melatonin late treatment RCT: 17% improved recovery (p=0.38).
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).

Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/fogleman

448 patient melatonin late treatment study: 54% lower mortality (p=0.0009).
Retrospective 2,463 hospitalized patients in Spain, 265 treated with melatonin, showing lower mortality with treatment in PSM analysis, however these results are subject to immortal time bias. Authors excluded from the sample patients that died during the first 72 hours of admission without taking melatonin, and patients that started on melatonin in the last 7 days of their admittance, having completed 75% of their stay.

Jul 2021, Sánchez-González, https://jcsm.aasm.org/doi/10.5664/jcsm.9554, https://c19p.org/sanchezgonzalez

40 patient melatonin late treatment study: 48% faster recovery (p=0.001).
40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.

May 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/abs/pii/S0014299921003460#, https://c19p.org/hosseini

60 patient melatonin early treatment study: 91% lower hospitalization (p=0.05).
Small study with 30 patients treated with melatonin, cannabidiol, and for 14 patients angiotensin 1-7, compared with an age/sex matched control group during the same period, showing lower hospitalization with treatment.

Dec 2020, J. Infectiology, https://www.infectiologyjournal.com/articles/covid-19-disease-as-an-acute-angiotensin-1-7-deficiency-a-preliminary-phase-2-study-with-angiotensin-1-7-in-association-with-melatonin-and-cannabidiol-in-symptomatic-covid19-infected-subjects, https://c19p.org/lissoni

20 patient melatonin ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.

Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darban

31 patient melatonin ICU study: 39% lower mortality (p=0.37), 43% shorter ventilation (p=0.13), and 2% shorter ICU admission (p=0.85).
Retrospective 31 ICU patients, 12 treated with melatonin, showing lower mortality with treatment, without statistical significance. Melatonin 15mg daily.

Mar 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122002527, https://c19p.org/karimpourrazkenari

58,562 patient melatonin late treatment study: 19% lower mortality (p=0.15).
Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was only in three age ranges and severe COVID was binary, likely leading to substantial residual confounding. Unadjusted differences were extreme with 60% >80 years old for melatonin compared to 15% for control. Mean daily dose 2.61mg. The title of the paper is incorrect, the most adjusted results show melatonin did reduce mortality (without reaching statistical significance).

Feb 2022, J. Travel Medicine, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab195/6523003, https://c19p.org/sanchezrico

67 patient melatonin ICU RCT: 4% lower mortality (p=0.73), 14% improved recovery (p=0.19), and 27% shorter ventilation (p=0.09).
RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.

May 2022, J. Taibah University Medical Sciences, https://www.sciencedirect.com/science/article/pii/S1658361222000877, https://c19p.org/alizadeh2

314 patient melatonin prophylaxis RCT: 108% more cases (p=0.26).
PrEP RCT healthcare workers in Spain, showing no significant difference in cases with melatonin prophylaxis. Most cases were asymptomatic or paucisymtomatic, there were two symptomatic cases, no moderate/severe cases, and no hospitalization. The registered primary outcome is symptomatic cases. Authors report on all cases due to the small number of symptomatic cases. They did not include the original primary outcome results in the paper, but have provided the results via email to a contributor. The dosage in this trial is very low, 2mg daily. Meta regression suggests higher doses are much more effective. EudraCT 2020-001530-35.

Feb 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/4/1139, https://c19p.org/garciagarcia
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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