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Melatonin COVID-19 studies. Recently added: Bologna Cecon. Submit updates/corrections.
Restrict:    All    Early    Late    Prophylaxis
Jan 14
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis)
Melatonin for COVID-19: real-time meta analysis of 12 studies
Details   • Statistically significant improvements are seen for mortality and recovery. 8 studies from 5 different countries show statistically significant improvements in isolation (6 for the most serious outcome). • Meta analysis using the most..
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 (Peer Reviewed)
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) (Peer Reviewed)
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 (Peer Reviewed)
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 (Peer Reviewed)
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) (Peer Reviewed)
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 (Peer Reviewed)
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 (Peer Reviewed) 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) (Peer Reviewed)
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 (Peer Reviewed)
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) (Peer Reviewed)
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 (Peer Reviewed)
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) (Peer Reviewed)
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 (Peer Reviewed)
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 (Peer Reviewed)
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) (Peer Reviewed)
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 (Peer Reviewed)
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 (Peer Reviewed) 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 (Peer Reviewed)
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 (Peer Reviewed)
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 (Peer Reviewed) 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 (Peer Reviewed)
cases, ↓58.0%, p<0.0001
Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing
Details   Retrospective 11,672 patients tested for COVID-19, 818 that tested positive, showing significantly lower risk with melatonin use.
Jun 4
Theory Hooper, P., Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9 (Peer Reviewed) (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) (Peer Reviewed)
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) (Peer Reviewed)
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) (Peer Reviewed)
COVID-19: Melatonin as a potential adjuvant treatment
Details   Review of the potential benefits of melatonin for COVID-19.
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