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Melatonin for COVID-19
18 studies with >14,000 patients
Serious outcome risk
Melatonin
Control
Significantly lower risk for mortality, ventilation, hospitalization, and recovery.
26% lower risk in 8 RCTs CI 3-44%
33% lower mortality in 10 studies CI 19-44%
COVID-19 Melatonin studies · October 2026
Melatonin was adopted in 1 country.
Covid Analysis Melatonin reduces COVID-19 risk: real-time meta-analysis of 18 studies (Version 29)
Significantly lower risk is seen for mortality, ventilation, hospitalization, and recovery. 10 studies from 10 independent teams in 6 countries show significant benefit. Meta-analysis using the most serious outcome reported shows..
Jul 21
2025
 Sánchez-García et al., Journal of Medical Virology, doi:10.1002/jmv.70807 Oral Melatonin in Critically Ill Patients With COVID‐19: A Quasi‐Experimental Pragmatic Trial
42% lower mortality (p=0.002), 54% lower ventilation (p=0.002), 31% shorter ICU admission (p=0.002), and 21% shorter hospitalization (p=0.007). Quasi-experimental study of 335 critically ill COVID-19 patients showing significantly lower 90-day mortality with high-dose oral melatonin (50-200mg daily). The study used alternating control and treatment periods, with 202 patients rece..
Jul 17
2025
 Chen et al., Redox Biology, doi:10.1016/j.redox.2025.103766 Viral mitochondriopathy in COVID-19
Discussion of the role of mitochondrial dysfunction in COVID-19 pathogenesis. Authors describe how SARS-CoV-2 viral proteins disrupt mitochondrial function through multiple mechanisms, including impairing bioenergetics, altering calcium h..
Jul 16
2025
 Tamanna et al., Scientific Reports, doi:10.1038/s41598-025-07170-8 Serum melatonin as a potential biomarker for COVID-19 severity
Retrospective 145 COVID-19 patients in South Korea showing significantly lower serum melatonin levels in patients with severe disease and in non-survivors compared to survivors.
May 19
2025
 Tian et al., British Journal of Clinical Pharmacology, doi:10.1002/bcp.70099 Association between ramelteon and 30-day mortality in ICU patients with COVID-19: A retrospective analysis of the MIMIC-IV database
47% lower mortality (p=0.005). PSM retrospective 1,066 ICU patients in China, showing significantly lower mortality with ramelteon treatment.
Jan 31
2025
 Qin et al., Clinics, doi:10.1016/j.clinsp.2025.100638 Benefits of melatonin on mortality in severe-to-critical COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials
Meta-analysis of 3 RCTs (451 patients) showing significantly lower in-hospital mortality with melatonin treatment in severe-to-critical COVID-19 patients. Authors propose melatonin's effectiveness stems from its antioxidant, anti-inflamma..
Jan 16
2025
 Sanduzzi Zamparelli et al., Life, doi:10.3390/life15010113 Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective
Review of immune-boosting and antiviral effects of antioxidants in COVID-19 pneumonia. Authors provide an overview of the literature on the use of antioxidants, including vitamins, trace elements, ozone, glutathione, L-carnitine, melatoni..
Dec 31
2024
 Acharya et al., Melatonin Research, doi:10.32794/mr112500181 Potential therapeutic intervention of melatonin against COVID-19: A comparative pharmacokinetic study
In silico study showing that melatonin may be beneficial for COVID-19 compared to methylprednisolone, doxycycline, oseltamivir, and remdesivir. Authors find that melatonin has superior pharmacokinetic properties, including higher bioavail..
Nov 8
2024
 Xie et al., Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6 The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death
Review of the effects of reactive oxygen species (ROS) on cell death pathways in SARS-CoV-2 infection. SARS-CoV-2 induces oxidative stress and ROS generation which can lead to several types of regulated cell death including NETosis, ferro..
Nov 5
2024
 Šeškutė et al., International Journal of Molecular Sciences, doi:10.3390/ijms252211872 Antiviral Effect of Melatonin on Caco-2 Cell Organoid Culture: Trick or Treat?
In vitro study showing that melatonin exhibits antiviral properties in gastrointestinal epithelial cells through modulation of type III interferon responses and cellular protection. Authors found that melatonin's effects varied based on t..
Jun 8
2024
 Amin et al., Microbes, Infection and Chemotherapy, doi:10.54034/mic.e1982 Role of Melatonin in Management of COVID-19: A Systematic Review
79% lower mortality (p=0.002) and 55% lower ICU admission (p=0.13). Meta analysis of 7 RCTs showing lower mortality and hospitalization time with melatonin treatment for COVID-19.
Jun 1
2024
 Zhao et al., Medicine Research, doi:10.21127/yaoyimr20240006 Melatonin Potentially Acts as a Widely-Acting Protective Tool in COVID-19
Review of melatonin for COVID-19. Authors highlight melatonin's role in potentially preventing, treating, and improving recovery from SARS-CoV-2 infection. Melatonin is suggested to boost resistance to COVID-19 by strengthening the immune..
Apr 19
2024
 Yehia et al., Molecular Neurodegeneration, doi:10.1186/s13024-024-00728-6 Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration
Review of melatonin as a potential ferroptosis inhibitor for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration. Authors propose that ferroptosis, an iron-dependent cell death triggered by lipid peroxidation, ma..
Apr 19
2024
 Chacin-Bonilla et al., Melatonin Research, doi:10.32794/mr112500168 Melatonin and viral infections: A review focusing on therapeutic effects and SARS-CoV-2
Review of the potential therapeutic effects of melatonin on viral infections, with a focus on SARS-CoV-2 and COVID-19. Authors highlight melatonin's potent anti-inflammatory, antioxidant, and immunomodulatory properties, which suggest its..
Jan 31
2024
 Soto et al., International Journal of Molecular Sciences, doi:10.3390/ijms25084543 (date from preprint) Redox Homeostasis Alteration Is Restored through Melatonin Treatment in COVID-19 Patients: A Preliminary Study
Prospective study of 17 hospitalized COVID-19 patients showing restored redox homeostasis, decreased oxidative stress, improved antioxidant enzyme activity, modulated glucose homeostasis, and inhibited Warburg effect with melatonin treatm..
Jan 26
2024
 Lempesis et al., International Journal of Molecular Medicine, doi:10.3892/ijmm.2024.5352 A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review)
Review of the therapeutic potential of melatonin for COVID-19 and long COVID. Authors provide an extensive review of melatonin's role in health and disease, covering antioxidant, anti-inflammatory, antiviral, and mitochondria-protective p..
Dec 21
2023
 Alomari et al., Reviews in Medical Virology, doi:10.1002/rmv.2499 Assessing the antiviral potential of melatonin: A comprehensive systematic review
Review of the antiviral potential of melatonin through analysis of in silico, in vitro, animal, and clinical studies. Authors identify 20 relevant studies showing evidence that melatonin has strong antiviral properties. In silico studies ..
Dec 15
2023
 Donzelli, A., MDPI AG, doi:10.20944/preprints202312.1178.v1 Neglected Effective Early Therapies against COVID-19: Focus on Functional Foods and Related Active Substances. A Review
Review of a group of compounds with efficacy shown in RCTs, safety, favorable opportunity costs, biological plausibility, and accessibility without major conflicts of interest. The compounds include curcumin, nigella sativa (black seed), ..
Sep 30
2023
 Molina-Carballo 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
2023
 Taha 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
2023
 Tóth 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
2023
 Mahjoub 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
2023
 Alobaidy 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
2023
 Langen, 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
2023
 Boukef 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 3 years after completion.
Feb 13
2023
 Karimi 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
 Ameri 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
 Wang 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
 Hosseinzadeh 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
 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 ..
Jul 23
2022
 Loh 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
 Pilia 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
 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 31
2022
 Fernandez-Tresguerres 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 4 years after completion.
Mar 22
2022
 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
2022
 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
2022
 Kory 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
 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
2022
 Reiter 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
 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..
Feb 1
2022
 Oral 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 4 years after completion.
Jan 31
2022
 Tan 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
 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
2022
 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
2022
 Cecon 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
 Menczel Schrire 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
 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 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 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 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, Journal of Clinical Sleep Medicine, doi:10.5664/jcsm.9554 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 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:10.31219/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
 Davoodian 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
 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 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 Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections
Review of melatonin for COVID-19, 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 influenza.
Mar 1
2021
 Piovezan 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 5 years after estimated completion.
Feb 9
2021
 Hancock 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.
Jan 3
2021
 Fernandes et al., Melatonin Research, doi:10.32794/mr11250090 Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers
In silico and rat study showing that higher lung melatonin synthesis (measured by MEL-Index) may predict asymptomatic SARS-CoV-2 carriers through negative correlation with viral entry and infection-related genes. Authors analyzed 288 heal..
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, showing no significant differences. This study has several data issues: The study reports a mean age of 59 ± 19 years with a range of 20-65 ..
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 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. Results are subject to immortal time bias and confounding by indication. Melatonin was prescribed to patients exhibiting insomnia, a..
Aug 5
2020
 Rodríguez-Rubio 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 5 years after completion.
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 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 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 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 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 COVID-19: Melatonin as a potential adjuvant treatment
Review of the potential benefits of melatonin for COVID-19.