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Dec 3 |
Melatonin for COVID-19: real-time meta analysis of 18 studies | |
| Statistically significant lower risk is seen for mortality, ventilation, and recovery. 9 studies from 9 independent teams in 5 countries show statistically significant improvements. • Meta analysis using the most serious outcome reporte.. | ||
Sep 30 |
et al., Melatonin Research, doi:10.32794/mr112500159 | The preventive and protective role of melatonin in SARS-CoV-2 infection: a retrospective study |
| Retrospective 62 patients taking relatively high doses of melatonin since before the pandemic, showing relatively low incidence of COVID-19, and relatively mild cases. There were 7 PCR+ cases, 3 asymptomatic, 3 mild, and one moderate. Pat.. | ||
Sep 22 |
et al., Advances in Medical Sciences, doi:10.1016/j.advms.2023.09.007 | Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: Systematic review and meta-analysis |
| Systematic review and meta analysis of 11 COVID-19 studies showing significantly higher clinical improvement and shorter hospitalization and mechanical ventilation time with melatonin treatment. | ||
Aug 16 |
et al., Signa Vitae, doi:10.22514/sv.2023.076 | Melatonin as adjuvant treatment in COVID-19 patients. A meta-analysis of randomized and propensity matched studies |
| 38% lower mortality (p=0.03). Meta analysis of seven melatonin RCTs and one propensity matched study for hospitalized COVID-19 patients, showing significantly lower mortality with treatment. | ||
Jun 20 |
et al., Explore, doi:10.1016/j.explore.2023.06.009 | Melatonin, vitamins and minerals supplements for the treatment of Covid-19 and Covid-like illness: a prospective, randomized, double-blind multicenter study. |
| 67% improved recovery (p=0.32). RCT 164 low-risk (no hospitalizations) patients in Tunisia, showing improved recovery with zinc, melatonin, and vitamins A-E. This study includes COVID-19 and COVID-like illness, with 49% of 128 patients receiving a PCR test being COVID-1.. | ||
May 24 |
et al., Molecular Biology Reports, doi:10.1007/s11033-023-08515-0 | Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19 |
| Analysis of 40 COVID-19 ICU patients and 40 matched healthy controls, showing significantly lower melatonin levels in COVID-19 patients. | ||
Mar 5 |
, M., Rounding The Earth | Melatonin - the Hormone of Both Sun and Darkness - Protects Your Health and Can Save Your Life |
| Extensive review of melatonin and the evidence of beneficial effects for many health issues including COVID-19. | ||
Feb 28 |
et al., NCT05670444 | Melatonin, Vitamins and Minerals Supplements for the Treatment of Covid-19 and Covid-like Illness: Results of a Prospective, Randomised, Double-blinded Multicentre Study |
| 150 patient melatonin early treatment RCT with results not reported over 9 months after completion. | ||
Feb 13 |
et al., Advances in Animal and Veterinary Sciences, doi:10.17582/journal.aavs/2023/11.3.404.409 | The Potential of Melatonin and N-Acetylcysteine on Remdesivir Induced Liver Injury in Covid 19 Patients |
| RCT 70 hospitalized COVID-19 patients evaluating the effects of N-acetylcysteine (NAC) and melatonin on liver injury induced by remdesivir treatment. NAC 600mg twice daily and melatonin 6mg daily. All patients received remdesivir. Liver e.. | ||
Nov 19 2022 |
et al., Inflammopharmacology, doi:10.1007/s10787-022-01096-7 | Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial |
| 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. | ||
Sep 30 2022 |
et al., Medicine, doi:10.1097/MD.0000000000030874 | 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 2022 |
et al., Life Sciences, doi:10.1016/j.lfs.2022.120866 | 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 2022 |
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 .. | ||
Jul 23 2022 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms23158122 | Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19 |
| Review of melatonin for viral infections and post-infection sequelae. The SARS-CoV-2 virus can cause oxidative stress, mitochondrial dysfunction, LINE1 derepression, and changes to m6A RNA modifications. These effects can increase viral r.. | ||
May 18 2022 |
et al., Annals of Medicine and Surgery, doi:10.1016/j.amsu.2022.103817 | 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 2022 |
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 31 2022 |
et al., NCT05596617 | Safety and Efficacy of Drugs Given Off-label for COVID-19 |
| 335 patient melatonin late treatment study with results not reported over 1.5 years after completion. | ||
Mar 22 2022 |
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 2022 |
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 2022 |
et al., Journal of Clinical Medicine Research, doi:10.14740/jocmr4658 | “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 2022 |
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 2022 |
et al., Cellular and Molecular Life Sciences, doi:10.1007/s00018-021-04102-3 | 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 2022 |
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.. | ||
Feb 1 2022 |
et al., NCT05318144 | Prognostic Value of Serum Melatonin as a Biomarker for the Determination of Severe COVID-19 Infection in Pregnant Women |
| 228 patient melatonin study with results not reported over 1.5 years after completion. | ||
Jan 31 2022 |
et al., Life Sciences, doi:10.1016/j.lfs.2022.120368 | 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 2022 |
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 2022 |
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 2022 |
et al., bioRxiv, doi:10.1101/2021.12.30.474561 | 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 19 2021 |
et al., Journal of Pineal Research, doi:10.1111/jpi.12782 | Safety of higher doses of melatonin in adults: A systematic review and meta-analysis |
| Safety analysis of 79 high-dose melatonin studies, finding that ≥10mg melatonin did not increase the frequency of SAEs across a range of clinical conditions. | ||
Dec 14 2021 |
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 |
et al., Science of The Total Environment, doi:10.1016/j.scitotenv.2021.152072 | 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 |
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 |
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 |
et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356 | 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 |
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 |
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 |
et al., Antioxidants, doi:10.3390/antiox10071152 | 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 |
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 |
et al., Journal of Inorganic Biochemistry, doi:10.1016/j.jinorgbio.2021.111546 | 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 |
, A., OSF Preprints, doi:0.31219/osf.io/xw3np | 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 |
et al., SSRN, doi:10.2139/ssrn.3878090 | 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. | ||
Jun 23 2021 |
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 |
et al., Endocrine Practice, doi:10.1016/j.eprac.2021.06.001 | 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 |
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 |
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 |
et al., Open Heart, doi:10.1136/openhrt-2020-001568 | 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.. | ||
Mar 1 2021 |
et al., NCT04470297 | Adjuvant Therapeutic Effects of Melatonin Agonist on Hospitalized Patients With Confirmed or Suspected COVID-19 |
| Estimated 100 patient melatonin late treatment RCT with results not reported over 2.5 years after estimated completion. | ||
Feb 9 2021 |
et al., SSRN, doi:10.2139/ssrn.3779211 | 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 |
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 |
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 |
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. | ||
Nov 6 2020 |
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 |
et al., medRxiv, doi:10.1101/2020.10.15.20213546 | 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. | ||
Aug 5 2020 |
et al., Trials, doi:10.1186/s13063-020-04632-4 | A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol for a randomized controlled trial |
| 18 patient melatonin late treatment RCT with results not reported over 3 years after completion. | ||
Jun 15 2020 |
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 |
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 |
, P., Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9 | 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 |
et al., Frontiers in Medicine, doi:10.3389/fmed.2020.00226 | 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 |
et al., SSRN, doi:10.2139/ssrn.3601861 | 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 |
et al., International Reviews of Immunology, doi:10.1080/08830185.2020.1756284 | Can melatonin reduce the severity of COVID-19 pandemic? |
| Review of the potential benefits of melatonin for COVID-19. | ||
Mar 23 2020 |
et al., Life Sciences, doi:10.1016/j.lfs.2020.117583 | COVID-19: Melatonin as a potential adjuvant treatment |
| Review of the potential benefits of melatonin for COVID-19. | ||
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