Melatonin for COVID-19: real-time analysis of all 9 studies

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Database of all melatonin COVID-19 studies. Submit updates/corrections.


Jul 20	Review	Ramos et al., Antioxidants, doi:10.3390/antiox10071152 (Review) (Peer Reviewed)	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	Details Source PDF Review 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
	Review of melatonin for COVID-19 discussing mechanisms of action and ongoing trials. Ramos et al., 7/20/2021, peer-reviewed, 10 authors.
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Jul 17	Review	Camp et al., Journal of Inorganic Biochemistry, doi:10.1016/j.jinorgbio.2021.111546 (Review) (Peer Reviewed)	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 17	Details Source PDF Review 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
	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. Camp et al., 7/17/2021, peer-reviewed, 5 authors.
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Jul 2	Theory	Sen, A., OSF Preprints, doi:0.31219/osf.io/xw3np (Preprint) (Theory)	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 2	Details Source PDF Theory Theory
	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. Sen et al., 7/2/2021, preprint, 1 author.
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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 23	Details Source PDF Late treatment study Late treatment study
	Farnoosh et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.06.006 (Peer Reviewed)
	Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial
	RCT 44 hospitalized patients in Iran, 24 treated with melatonin, showing faster recovery with treatment. There was no mortality. risk of ICU admission, 81.5% lower, RR 0.19, p = 0.20, treatment 0 of 24 (0.0%), control 2 of 20 (10.0%), continuity correction due to zero event. recovery time, 49.0% lower, relative time 0.51, p = 0.004, treatment 24, control 20. risk of no hospital discharge, 44.4% lower, RR 0.56, p = 0.65, treatment 2 of 24 (8.3%), control 3 of 20 (15.0%). time to viral-, 42.9% lower, relative time 0.57, p = 0.02, treatment 24, control 20. Farnoosh et al., 6/23/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 12 authors.
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Jun 10	Review	Cross et al., Endocrine Practice, doi:10.1016/j.eprac.2021.06.001 (Review) (Peer Reviewed)	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.
Jun 10	Details Source PDF Review 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
	Review of the potential benefits of melatonin for COVID-19. Cross et al., 6/10/2021, peer-reviewed, 4 authors.
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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 29	Details Source PDF Early treatment study Early treatment study
	Alizadeh et al., Iranian Journal of Allergy, Asthma and Immunology (Peer Reviewed)
	A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement
	Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment. risk of no recovery, 73.0% lower, RR 0.27, p = 0.06, treatment 2 of 14 (14.3%), control 9 of 17 (52.9%), day 14. Alizadeh et al., 5/29/2021, Single Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 6 authors.
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May 17	Late	Hosseini et al., European Journal of Pharmacology, doi:10.1016/j.ejphar.2021.174193 (Peer Reviewed)		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 that melatonin attenuated inflammatory cytokines.
May 17	Details Source PDF Late treatment study Late treatment study
	Hosseini et al., European Journal of Pharmacology, doi:10.1016/j.ejphar.2021.174193 (Peer Reviewed)
	Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment
	40 hospitalized patients in Iran, 20 treated with melatonin, showing that melatonin attenuated inflammatory cytokines. Hosseini et al., 5/17/2021, peer-reviewed, 9 authors.
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Mar 19	Review	DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001568 (Review) (Peer Reviewed)	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..
Mar 19	Details Source PDF Review 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
	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 influenza. DiNicolantonio et al., 3/19/2021, peer-reviewed, 3 authors.
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Dec 23 2020	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 23 2020	Details Source PDF Late treatment study Late treatment study
	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
	Review of melatonin for COVID-19 along with preliminary data suggesting efficacy of melatonin for COVID-19 pneumonia patients. Brusco et al., 12/23/2020, peer-reviewed, 6 authors.
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Dec 15 2020	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.
Dec 15 2020	Details Source PDF Late treatment study Late treatment study
	Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 (Peer Reviewed)
	Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
	Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52. risk of disease progression, 33.3% lower, RR 0.67, p = 1.00, treatment 2 of 10 (20.0%), control 3 of 10 (30.0%). ICU time, 6.0% lower, relative time 0.94, p = 0.30, treatment 10, control 10. Darban et al., 12/15/2020, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with vitamin C and zinc) - results of individual treatments may vary.
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Nov 6 2020	PrEP	Zhou et al., PLOS Biology, doi:10.1371/journal.pbio.3000970 (Peer Reviewed)	cases, ↓21.1%, p=0.0005	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.
Nov 6 2020	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Zhou et al., PLOS Biology, doi:10.1371/journal.pbio.3000970 (Peer Reviewed)
	A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
	PSM observational study with a database of 26,779 patients in the USA, showing significantly lower risk of PCR+ with melatonin usage. risk of COVID-19 case, 21.1% lower, RR 0.79, p < 0.001, treatment 222 of 1055 (21.0%), control 8052 of 25724 (31.3%), OR converted to RR, PSM. Zhou et al., 11/6/2020, retrospective, propensity score matching, USA, North America, peer-reviewed, 18 authors.
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Oct 18 2020	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.
Oct 18 2020	Details Source PDF Late treatment study Late treatment study
	Ramlall et al., medRxiv, doi:10.1101/2020.10.15.20213546 (Preprint)
	Melatonin is significantly associated with survival of intubated COVID-19 patients
	Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment. risk of death, 86.9% lower, RR 0.13, p < 0.001, treatment 196, control 752, multivariate model Cox proportional hazards. Ramlall et al., 10/18/2020, retrospective, USA, North America, preprint, 3 authors.
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Jun 15 2020	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 15 2020	Details Source PDF Late treatment study Late treatment study
	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
	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. None required mechanical ventilation. Castillo et al., 6/15/2020, retrospective, Philippines, Asia, peer-reviewed, 10 authors.
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Jun 10 2020	PrEP	Jehi et al., Chest, doi:10.1016/j.chest.2020.05.580 (Peer Reviewed)	cases, ↓58.2%, 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 10 2020	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Jehi et al., Chest, doi:10.1016/j.chest.2020.05.580 (Peer Reviewed)
	Individualizing Risk Prediction for Positive Coronavirus Disease 2019 Testing
	Retrospective 11,672 patients tested for COVID-19, 818 that tested positive, showing significantly lower risk with melatonin use. risk of COVID-19 case, 58.2% lower, RR 0.42, p < 0.001, treatment 16 of 532 (3.0%), control 802 of 11140 (7.2%), development cohort. risk of COVID-19 case, 99.7% lower, RR 0.003, p = 0.09, treatment 0 of 18 (0.0%), control 290 of 2005 (14.5%), continuity correction due to zero event, Florida validation cohort. Jehi et al., 6/10/2020, retrospective, USA, North America, peer-reviewed, 8 authors.
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May 15 2020	Review	Reiter et al., Frontiers in Medicine, doi:10.3389/fmed.2020.00226 (Review) (Peer Reviewed)	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 15 2020	Details Source PDF Review 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
	Review of melatonin's action as an antiinflammatory, antioxidant, and antiviral (against other viruses) agent, and proposed therapeutic algorithm for use with COVID-19. Reiter et al., 5/15/2020, peer-reviewed, 4 authors.
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May 4 2020	Review	Charaa et al., SSRN, doi:10.2139/ssrn.3601861 (Review) (Preprint)	review	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.
May 4 2020	Details Source PDF Review Review
	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. Charaa et al., 5/4/2020, preprint, 4 authors.
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Apr 29 2020	Review	Shneider et al., International Reviews of Immunology, doi:10.1080/08830185.2020.1756284 (Review) (Peer Reviewed)	review	Can melatonin reduce the severity of COVID-19 pandemic?
	Details Review of the potential benefits of melatonin for COVID-19.
Apr 29 2020	Details Source PDF Review 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?
	Review of the potential benefits of melatonin for COVID-19. Shneider et al., 4/29/2020, peer-reviewed, 3 authors.
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Mar 23 2020	Review	Zhang et al., Life Sciences, doi:10.1016/j.lfs.2020.117583 (Review) (Peer Reviewed)	review	COVID-19: Melatonin as a potential adjuvant treatment
	Details Review of the potential benefits of melatonin for COVID-19.
Mar 23 2020	Details Source PDF Review Review
	Zhang et al., Life Sciences, doi:10.1016/j.lfs.2020.117583 (Review) (Peer Reviewed)
	COVID-19: Melatonin as a potential adjuvant treatment
	Review of the potential benefits of melatonin for COVID-19. Zhang et al., 3/23/2020, peer-reviewed, 8 authors.
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