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Other Treatments Global Adoption
 
Melatonin COVID-19 studies. Recent:
Wang
Hosseinzadeh
Fogleman.
Melatonin has been officially adopted for early treatment in part of 1 country. Submit updates/corrections.
Oct 4
Covid Analysis (Preprint) (meta analysis) Melatonin for COVID-19: real-time meta analysis of 17 studies
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..
Sep 30
Wang et al., Medicine, doi:10.1097/MD.0000000000030874 (meta analysis) The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis
67% improved recovery [p=0.003]. Systematic review and meta analysis of 6 melatonin studies showing significant improvement in recovery.
Aug 6
Hosseinzadeh et al., Life Sciences, doi:10.1016/j.lfs.2022.120866 (Review) Melatonin effect on platelets and coagulation: Implications for a prophylactic indication in COVID-19
Review of the mechanisms and potential benefits of melatonin against coagulopathy induced by SARS-CoV-2 infection.
Jul 27
Fogleman et al., The Journal of the American Board of Family Medicine, doi:10.3122/jabfm.2022.04.210529 A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19
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 ..
May 18
Pilia et al., Annals of Medicine and Surgery, doi:10.1016/j.amsu.2022.103817 (meta analysis) Does melatonin reduce mortality in COVID-19?
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
Alizadeh et al., Journal of Taibah University Medical Sciences, doi:10.1016/j.jtumed.2022.04.012 High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial
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.
Mar 22
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
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
Karimpour-razkenari et al., Annals of Medicine and Surgery, doi:10.1016/j.amsu.2022.103492 Melatonin as adjunctive therapy in patients admitted to the Covid-19
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.
Feb 24
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
Review of the data supporting the MATH+ hospital treatment protocol for COVID-19.
Feb 21
García-García et al., Journal of Clinical Medicine, doi:10.3390/jcm11041139 Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial
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 hospitalizati..
Feb 20
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
Review of the clinical evidence and mechanisms of action supporting the use of melatonin for COVID-19.
Feb 5
Sánchez-Rico et al., Journal of Travel Medicine, doi:10.1093/jtm/taab195 Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational 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..
Jan 31
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
Review of the mechanisms of action and clinical evidence supporting the use of melatonin for severe COVID-19.
Jan 25
Kumar Yadalam et al., Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2022.01.049 Assessing the therapeutic potential of angomelatine, ramelteon, and melatonin against SARS-Cov-2
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
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
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
Cecon et al., bioRxiv, doi:10.1101/2021.12.30.474561 (Preprint) Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
K18-hACE2 mouse study showing treatment with melatonin and derived drugs agomelatine and ramelteon inhibited SARS-CoV-2 infection in the brain.
Dec 14
2021
Bologna et al., Journal of Clinical Medicine, doi:10.3390/jcm10245857 Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational 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..
Dec 1
2021
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
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
2021
Hasan et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.10.012 The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients
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.
Sep 29
2021
Cecon et al., Journal of Pineal Research, doi:10.1111/jpi.12772 Therapeutic potential of melatonin and melatonergic drugs on K18-hACE2 mice infected with SARS-CoV-2
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
2021
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
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
2021
Mousavi et al., Journal of Medical Virology, doi:10.1002/jmv.27312 Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial
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 5
2021
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
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
2021
Ramos et al., Antioxidants, doi:10.3390/antiox10071152 (Review) The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy
Review of melatonin for COVID-19 discussing mechanisms of action and ongoing trials.
Jul 20
2021
Sánchez-González What if melatonin could help COVID-19 severe patients?
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 tha..
Jul 17
2021
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
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
2021
Sen, A., OSF Preprints, doi:0.31219/osf.io/xw3np (Preprint) (Theory) Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis
Proposal that melatonin deficiency plays a significant role in COVID-19 associated mucormycosis.
Jul 1
2021
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
RCT 81 hospitalized patients in Iran, showing significantly improved oxygen saturation with treatment. Melatonin 3mg, 3x daily for 2 weeks. IRCT20200408046988N1.
Jun 23
2021
Farnoosh et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.06.006 Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial
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 10
2021
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
Review of the potential benefits of melatonin for COVID-19.
May 29
2021
Alizadeh et al., Iranian Journal of Allergy, Asthma and Immunology A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement
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 17
2021
Hosseini et al., European Journal of Pharmacology, doi:10.1016/j.ejphar.2021.174193 Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment
48% faster recovery [p=0.001]. 40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.
Mar 19
2021
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
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
2021
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
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
2020
Lissoni et al., Journal of Infectiology, doi:10.29245/2689-9981/2018/2.1162 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
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 23
2020
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
Review of melatonin for COVID-19 along with preliminary data suggesting efficacy of melatonin for COVID-19 pneumonia patients.
Dec 15
2020
Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
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. IRCT20151228025732N52.
Nov 6
2020
Zhou et al., PLOS Biology, doi:10.1371/journal.pbio.3000970 A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
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.
Oct 18
2020
Ramlall et al., medRxiv, doi:10.1101/2020.10.15.20213546 (Preprint) Melatonin is significantly associated with survival of intubated COVID-19 patients
87% lower mortality [p<0.0001]. Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment.
Jun 15
2020
Castillo et al., Melatonin Research, doi:10.32794/mr11250063 Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series
94% lower mortality [p=0.08], 89% lower ventilation [p=0.32], and 34% shorter hospitalization. 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
2020
Jehi et al., Chest, doi:10.1016/j.chest.2020.05.580 Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing
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 4
2020
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
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
2020
Reiter et al., Frontiers in Medicine, doi:10.3389/fmed.2020.00226 (Review) Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19
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
2020
Charaa et al., SSRN, doi:10.2139/ssrn.3601861 (Review) (Preprint) Prophylactic Treatment Protocol against the Severity of COVID-19 Using Melatonin
Review of the potential benefits of melatonin for COVID-19, and a proposed prophylactic treatment protocol.
Apr 29
2020
Shneider et al., International Reviews of Immunology, doi:10.1080/08830185.2020.1756284 (Review) Can melatonin reduce the severity of COVID-19 pandemic?
Review of the potential benefits of melatonin for COVID-19.
Mar 23
2020
Zhang et al., Life Sciences, doi:10.1016/j.lfs.2020.117583 (Review) COVID-19: Melatonin as a potential adjuvant treatment
Review of the potential benefits of melatonin for COVID-19.
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