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Other Treatments Global Adoption
Melatonin COVID-19 studies. Recent:
Melatonin has been officially adopted for early treatment in part of 1 country. Submit updates/corrections.
May 26
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis)
Melatonin for COVID-19: real-time meta analysis of 16 studies
Details   • Statistically significant improvements are seen for mortality, ventilation, and recovery. 8 studies from 8 independent teams in 5 different countries show statistically significant improvements in isolation (6 for the most serious outco..
May 18
Meta Pilia et al., Annals of Medicine and Surgery, doi:10.1016/j.amsu.2022.103817 (meta analysis)
Does melatonin reduce mortality in COVID-19?
Details   Meta analysis of 3 melatonin RCTs showing significantly lower mortality with treatment. Authors note the small sample size in RCTs reporting mortality results to date.
May 13
Late Alizadeh et al., Journal of Taibah University Medical Sciences, doi:10.1016/j.jtumed.2022.04.012
death, ↓3.8%, p=0.73
High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial
Details   RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.
Mar 22
PrEPPEP Valiensi et al., Vertex Rev Arg Psiquiatr, 33:155 Pre-pandemic melatonin treatment for sleep disorders and COVID-19 infection. A retrospective cross-sectional study
Details   Retrospective 110 patients in Argentina treated with melatonin. Authors conclude that the results are consistent with melatonin being protective for COVID-19. The mean dose for positive patients was lower, 32.9 vs. 48.4mg/day, p = 0.10.
Mar 10
Late Karimpour-razkenari et al., Annals of Medicine and Surgery, doi:10.1016/j.amsu.2022.103492
death, ↓39.0%, p=0.37
Melatonin as adjunctive therapy in patients admitted to the Covid-19
Details   Retrospective 31 ICU patients, 12 treated with melatonin, showing lower mortality with treatment, without statistical significance. Melatonin 15mg daily.
Feb 24
Review Kory et al., Journal of Clinical Medicine Research, doi:10.14740/jocmr4658 (Review)
“MATH+” Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale
Details   Review of the data supporting the MATH+ hospital treatment protocol for COVID-19.
Feb 21
PrEPPEP García-García et al., Journal of Clinical Medicine, doi:10.3390/jcm11041139
symp. case, ↓7.4%, p=1.00
Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial
Details   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 hospitalizati..
Feb 20
Review Reiter et al., Cellular and Molecular Life Sciences, doi:10.1007/s00018-021-04102-3 (Review)
Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection
Details   Review of the clinical evidence and mechanisms of action supporting the use of melatonin for COVID-19.
Feb 5
Late Sánchez-Rico et al., Journal of Travel Medicine, doi:10.1093/jtm/taab195
death, ↓19.0%, p=0.15
Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study
Details   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..
Jan 31
Review Tan et al., Life Sciences, doi:10.1016/j.lfs.2022.120368 (Review)
Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality
Details   Review of the mechanisms of action and clinical evidence supporting the use of melatonin for severe COVID-19.
Jan 25
In Silico Kumar Yadalam et al., Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2022.01.049
In Silico
Assessing the therapeutic potential of angomelatine, ramelteon, and melatonin against SARS-Cov-2
Details   In Silico study of melatonin, angomelatine, and ramelteon for SARS-CoV-2, predicting significant SARS-CoV-2 RBD and ACE2 binding with all three.
Jan 14
Meta Lan et al., Journal of Medical Virology, doi:10.1002/jmv.27595
Efficacy of Melatonin in the Treatment of Patients With COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Details   Systematic review and meta analysis including 3 of the 5 melatonin RCTs at the time, showing significantly higher recovery with treatment, and lower ICU admission and mortality without statistical significance. The analysis only includes ..
Jan 3
Animal Cecon et al., bioRxiv, doi:10.1101/2021.12.30.474561 (Preprint)
animal study
Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
Details   K18-hACE2 mouse study showing treatment with melatonin and derived drugs agomelatine and ramelteon inhibited SARS-CoV-2 infection in the brain.
Dec 14
Late Bologna et al., Journal of Clinical Medicine, doi:10.3390/jcm10245857
death, ↓50.0%, p=0.48
Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study
Details   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..
Dec 1
Review Behl et al., Science of The Total Environment, doi:10.1016/j.scitotenv.2021.152072 (Review)
CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target
Details   Review of the cluster of differentiation 147 (CD147) transmembrane protein as an entry route for SARS-CoV-2, correlation with observed characteristics of COVID-19, and relevant potential therapeutics including azithromycin, melatonin, sta..
Oct 12
Late Hasan et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.10.012
death, ↓92.9%, p=0.0004
The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients
Details   RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment.
Sep 29
Animal Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772
animal study
Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2
Details   Study of melatonin and melatonergic compounds with mice expressing the human ACE2 receptor (K18-hACE2). Daily administration of melatonin, agomelatine or ramelteon delayed the occurrence of severe clinical outcome with improvement of surv..
Sep 22
Review Castle et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356 (Review)
Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation
Details   Review of the effects of COVID-19 on inflammatory markers, and the effects on those markers of standard treatments vs. vitamin D, melatonin, and meditation, showing comparable or superior effects with the non-standard treatments. The stan..
Aug 30
Late Mousavi et al., Journal of Medical Virology, doi:10.1002/jmv.27312
death, ↓66.7%, p=0.62
Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial
Details   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 5
Late Ghaleh et al., Zeitschrift für Naturforschung C, doi:10.1515/znc-2021-0101 NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement
Details   Study of melatonin treatment in COVID-19 hospitalized patients showing anti-oxidative and anti-inflammatory activity, and beneficial impacts on lung cytokine storm.
Jul 20
Review Ramos et al., Antioxidants, doi:10.3390/antiox10071152 (Review)
The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy
Details   Review of melatonin for COVID-19 discussing mechanisms of action and ongoing trials.
Jul 20
Late Sánchez-González
death, ↓54.4%, p=0.0009
What if melatonin could help COVID-19 severe patients?
Details   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 tha..
Jul 17
Review Camp et al., Journal of Inorganic Biochemistry, doi:10.1016/j.jinorgbio.2021.111546 (Review)
Melatonin interferes with COVID-19 at several distinct ROS-related steps
Details   Review discussing how melatonin may improve COVID-19 prognosis by acting to reduce oxygen deficiency and hypoxia, vitamin B12 deficiency, NO deficiency, oxidative stress, and sleep disturbance.
Jul 2
Theory Sen, A., OSF Preprints, doi:0.31219/ (Preprint) (Theory)
Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis
Details   Proposal that melatonin deficiency plays a significant role in COVID-19 associated mucormycosis.
Jul 1
Late Davoodian et al., SSRN, doi:10.2139/ssrn.3878090 (Preprint) The Effect of Melatonin as an Adjuvant Therapy on COVID-19: A Randomized Clinical Trial
Details   RCT 81 hospitalized patients in Iran, showing significantly improved oxygen saturation with treatment. Melatonin 3mg, 3x daily for 2 weeks. IRCT20200408046988N1.
Jun 23
Late Farnoosh et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.06.006
ICU, ↓81.5%, p=0.20
Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial
Details   RCT 44 hospitalized patients in Iran, 24 treated with melatonin, showing faster recovery with treatment. There was no mortality.
Jun 10
Review Cross et al., Endocrine Practice, doi:10.1016/j.eprac.2021.06.001 (Review)
Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy
Details   Review of the potential benefits of melatonin for COVID-19.
May 29
Early Alizadeh et al., Iranian Journal of Allergy, Asthma and Immunology
no recov., ↓73.0%, p=0.06
A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement
Details   Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment.
May 17
Late Hosseini et al., European Journal of Pharmacology, doi:10.1016/j.ejphar.2021.174193
recov. time, ↓47.6%, p=0.001
Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment
Details   40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.
Mar 19
Review DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001568 (Review)
Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections
Details   Review of melatonin for COVID-19 and the result of Ramlall et al., suggesting that vitamin D, zinc, and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and infl..
Feb 9
PrEPPEP Hancock et al., SSRN, doi:10.2139/ssrn.3779211 (Preprint) Case Cluster of RT-PCR COVID-19 Positive Patients with an Unexpected Benign Clinical Course With Vitamin D, Melatonin, Vitamin C, and Viscum Album
Details   Case series of 24 COVID-19 patients (12 confirmed PCR+) treated with vitamin D, vitamin C, and melatonin, showing positive outcomes with no patient having worse than a mild case, including 7 high risk patients.
Dec 30
Early Lissoni et al., Journal of Infectiology, doi:10.29245/2689-9981/2018/2.1162
hosp., ↓90.9%, p=0.05
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
Details   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 23
Late Brusco et al., Melatonin Research, doi:10.32794/mr11250089 Efficacy of melatonin in non-intensive care unit patients with COVID-19 pneumonia and sleep dysregulation
Details   Review of melatonin for COVID-19 along with preliminary data suggesting efficacy of melatonin for COVID-19 pneumonia patients.
Dec 15
Late Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182
progression, ↓33.3%, p=1.00
Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
Details   Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52.
Nov 6
PrEPPEP Zhou et al., PLOS Biology, doi:10.1371/journal.pbio.3000970
cases, ↓21.1%, p=0.01
A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
Details   PSM observational study with a database of 26,779 patients in the USA, showing significantly lower risk of PCR+ with melatonin usage.
Oct 18
Late Ramlall et al., medRxiv, doi:10.1101/2020.10.15.20213546 (Preprint)
death, ↓86.9%, p<0.0001
Melatonin is significantly associated with survival of intubated COVID-19 patients
Details   Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment.
Jun 15
Late Castillo et al., Melatonin Research, doi:10.32794/mr11250063
death, ↓93.5%, p=0.08
Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series
Details   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. ..
Jun 10
PrEPPEP Jehi et al., Chest, doi:10.1016/j.chest.2020.05.580
cases, ↓58.0%, p<0.0001
Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing
Details   Retrospective 11,672 patients tested for COVID-19 with 818 testing positive, showing significantly lower risk with melatonin use.
Jun 4
Theory Hooper, P., Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9 (Theory)
COVID-19 and heme oxygenase: novel insight into the disease and potential therapies
Details   Proposal that COVID-19 risk is related to low intracellular heme oxygenase (HO-1), and that therapies that raise HO-1 may be beneficial, which includes fluvoxamine, certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins..
May 15
Review Reiter et al., Frontiers in Medicine, doi:10.3389/fmed.2020.00226 (Review)
Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19
Details   Review of melatonin's action as an antiinflammatory, antioxidant, and antiviral (against other viruses) agent, and proposed therapeutic algorithm for use with COVID-19.
May 4
Review Charaa et al., SSRN, doi:10.2139/ssrn.3601861 (Review) (Preprint)
Prophylactic Treatment Protocol against the Severity of COVID-19 Using Melatonin
Details   Review of the potential benefits of melatonin for COVID-19, and a proposed prophylactic treatment protocol.
Apr 29
Review Shneider et al., International Reviews of Immunology, doi:10.1080/08830185.2020.1756284 (Review)
Can melatonin reduce the severity of COVID-19 pandemic?
Details   Review of the potential benefits of melatonin for COVID-19.
Mar 23
Review Zhang et al., Life Sciences, doi:10.1016/j.lfs.2020.117583 (Review)
COVID-19: Melatonin as a potential adjuvant treatment
Details   Review of the potential benefits of melatonin for COVID-19.
Please send us corrections, updates, or comments. Vaccines and treatments are both valuable and complementary. All practical, effective, and safe means should be used. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases mortality, morbidity, collateral damage, and the risk of endemic status. 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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