Summary of COVID-19 melatonin studies

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

2. Hasan et al., The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients

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

3. Farnoosh et al., Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial

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

4. Jehi et al., Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing

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

5. Bologna et al., Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study

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

6. Ramlall et al., Melatonin is significantly associated with survival of intubated COVID-19 patients

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

7. Zhou et al., A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19

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

8. Mousavi et al., Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial

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

9. Alizadeh et al., A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement

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

10. Fogleman et al., A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

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

11. Sánchez-González et al., What if melatonin could help COVID-19 severe patients?

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

12. Hosseini et al., Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment

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

13. Lissoni et al., 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

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

14. Darban et al., Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial

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

15. Karimpour-razkenari et al., Melatonin as adjunctive therapy in patients admitted to the Covid-19

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

16. Sánchez-Rico et al., Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study

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

17. Alizadeh et al., High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial

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

18. García-García et al., Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial

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

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