{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:53:37Z","timestamp":1787662417473,"version":"build-2736575974"},"reference-count":96,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melatonin is registered to treat circadian rhythm sleep\u2013wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.<\/jats:p>","DOI":"10.3390\/ijms22168623","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T04:56:22Z","timestamp":1628657782000},"page":"8623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Melatonin as a Potential Adjuvant Treatment for COVID-19 beyond Sleep Disorders"],"prefix":"10.3390","volume":"22","author":[{"given":"Adam","family":"Wichniak","sequence":"first","affiliation":[{"name":"Third Department of Psychiatry and Sleep Medicine Center, Institute of Psychiatry and Neurology, 02-957 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5181-4360","authenticated-orcid":false,"given":"Aleksander","family":"Kania","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, 2nd Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-2912","authenticated-orcid":false,"given":"Mariusz","family":"Siemi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-8454","authenticated-orcid":false,"given":"Wies\u0142aw Jerzy","family":"Cuba\u0142a","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","first-page":"678164","article-title":"The Bidirectional Relationship between Sleep and Immunity against Infections","volume":"2015","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.5665\/sleep.4968","article-title":"Behaviorally Assessed Sleep and Susceptibility to the Common Cold","volume":"38","author":"Prather","year":"2015","journal-title":"Sleep"},{"key":"ref_3","first-page":"1063","article-title":"Sleep and Antibody Response to Hepatitis B Vaccination","volume":"35","author":"Prather","year":"2012","journal-title":"Sleep"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s12529-020-09879-4","article-title":"Temporal Links between Self-Reported Sleep and Antibody Responses to the Influenza Vaccine","volume":"28","author":"Prather","year":"2021","journal-title":"Int. J. Behav. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3934\/Neuroscience.2018.5.1","article-title":"Emotion, Emotion Regulation and Sleep: An Intimate Relationship","volume":"5","author":"Vandekerckhove","year":"2018","journal-title":"AIMS Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1468-1331.2011.03590.x","article-title":"The Economic Cost of Brain Disorders in Europe","volume":"19","author":"Olesen","year":"2012","journal-title":"Eur. J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/jsr.12594","article-title":"European Guideline for the Diagnosis and Treatment of Insomnia","volume":"26","author":"Riemann","year":"2017","journal-title":"J. Sleep Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.12740\/PP\/58771","article-title":"Prevalence of Self-Reported Insomnia in General Population of Poland","volume":"50","author":"Nowicki","year":"2016","journal-title":"Psychiatr. Pol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xue, Z., Lin, L., Zhang, S., Gong, J., Liu, J., and Lu, J. (2020). Sleep Problems and Medical Isolation during the SARS-CoV-2 Outbreak. Sleep Med., 112\u2013115.","DOI":"10.1016\/j.sleep.2020.04.014"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13119","DOI":"10.1111\/jsr.13119","article-title":"Covid-19 Health Crisis and Lockdown Associated with High Level of Sleep Complaints and Hypnotic Uptake at the Population Level","volume":"30","author":"Beck","year":"2021","journal-title":"J. Sleep Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-Month Neurological and Psychiatric Outcomes in 236\u2009379 Survivors of COVID-19: A Retrospective Cohort Study Using Electronic Health Records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Altena, E., Baglioni, C., Espie, C.A., Ellis, J., Gavriloff, D., Holzinger, B., Schlarb, A., Frase, L., Jernel\u00f6v, S., and Riemann, D. (2020). Dealing with Sleep Problems during Home Confinement Due to the COVID-19 Outbreak: Practical Recommendations from a Task Force of the European CBT-I Academy. J. Sleep Res.","DOI":"10.1111\/jsr.13052"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110687","DOI":"10.1016\/j.mce.2019.110687","article-title":"Temporal Organization of Pineal Melatonin Signaling in Mammals","volume":"503","author":"Gorman","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"793","DOI":"10.12740\/PP\/OnlineFirst\/66810","article-title":"Treatment Guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, Assessment and Therapeutic Methods","volume":"51","author":"Wichniak","year":"2017","journal-title":"Psychiatr. Pol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.5664\/jcsm.5100","article-title":"Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-","volume":"11","author":"Auger","year":"2015","journal-title":"J. Clin. Sleep Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"815","DOI":"10.12740\/PP\/68918","article-title":"Treatment Guidelines for Circadian Rhythm Sleep\u2014Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part II. Diagnosis and Treatment","volume":"51","author":"Wichniak","year":"2017","journal-title":"Psychiatr. Pol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1185\/03007995.2010.537317","article-title":"Prolonged Release Melatonin in the Treatment of Primary Insomnia: Evaluation of the Age Cut-off for Short- and Long-Term Response","volume":"27","author":"Wade","year":"2011","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mason, R.J. (2020). Pathogenesis of COVID-19 from a Cell Biology Perspective. Eur. Respir. J.","DOI":"10.1183\/13993003.00607-2020"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1016\/j.ajem.2020.09.054","article-title":"Non-Respiratory Presentations of COVID-19, a Clinical Review","volume":"38","author":"AlSamman","year":"2020","journal-title":"Am. J. Emerg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1038\/s41379-020-0603-3","article-title":"A Systematic Review of Pathological Findings in COVID-19: A Pathophysiological Timeline and Possible Mechanisms of Disease Progression","volume":"33","author":"Polak","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, Y., Lu, X., Li, Y., Chen, H., Chen, T., Su, N., Huang, F., Zhou, J., Zhang, B., and Yan, F. (2020). Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am. J. Respir. Crit. Care Med., 1430\u20131434.","DOI":"10.1164\/rccm.202003-0736LE"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chalmers, J.D., Crichton, M.L., Goeminne, P.C., Cao, B., Humbert, M., Shteinberg, M., Antoniou, K.M., Ulrik, C.S., Parks, H., and Wang, C. (2021). Management of Hospitalized Adults with Coronavirus Disease 2019 (COVID-19): A European Respiratory Society Living Guideline. Eur. Respir. J., 57.","DOI":"10.1183\/13993003.00048-2021"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sun, Q., Qiu, H., Huang, M., and Yang, Y. (2020). Lower Mortality of COVID-19 by Early Recognition and Intervention: Experience from Jiangsu Province. Ann. Intensive Care, 33.","DOI":"10.1186\/s13613-020-00650-2"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kleszczy\u0144ski, K., Slominski, A.T., Steinbrink, K., and Reiter, R.J. (2020). Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed. Nutrients, 12.","DOI":"10.3390\/nu12092561"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cardinali, D.P., Brown, G.M., and Pandi-Perumal, S.R. (2020). Can Melatonin Be a Potential \u201cSilver Bullet\u201d in Treating COVID-19 Patients?. Diseases, 8.","DOI":"10.3390\/diseases8040044"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/08830185.2020.1756284","article-title":"Can Melatonin Reduce the Severity of COVID-19 Pandemic?","volume":"39","author":"Shneider","year":"2020","journal-title":"Int. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"206","DOI":"10.32794\/mr11250091","article-title":"An Urgent Proposal for the Immediate Use of Melatonin as an Adjuvant to Anti- SARS-CoV-2 Vaccination","volume":"4","author":"Cardinali","year":"2021","journal-title":"Melatonin Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3892\/etm.2021.9659","article-title":"Effects of Melatonin on Protecting against Lung Injury (Review)","volume":"21","author":"Wang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fmed.2020.00226","article-title":"Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19","volume":"7","author":"Reiter","year":"2020","journal-title":"Front. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.sleep.2020.01.019","article-title":"The Role of Melatonin and Melatonin Receptor Agonist in the Prevention of Sleep Disturbances and Delirium in Intensive Care Unit\u2014A Clinical Review","volume":"69","author":"Lewandowska","year":"2020","journal-title":"Sleep Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mihardja, M., Roy, J., Wong, K.Y., Aquili, L., Heng, B.C., Chan, Y.S., Fung, M.L., and Lim, L.W. (2020). Therapeutic Potential of Neurogenesis and Melatonin Regulation in Alzheimer\u2019s Disease. Ann. N. Y. Acad. Sci., 43\u201362.","DOI":"10.1111\/nyas.14436"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Behn, C., and De Gregorio, N. (2020). Melatonin Relations with Energy Metabolism as Possibly Involved in Fatal Mountain Road Traffic Accidents. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062184"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Otamas, A., Grant, P.J., and Ajjan, R.A. (2020). Diabetes and Atherothrombosis: The Circadian Rhythm and Role of Melatonin in Vascular Protection. Diabetes Vasc. Dis. Res.","DOI":"10.1177\/1479164120920582"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"MacDonald, I.J., Huang, C.C., Liu, S.C., and Tang, C.H. (2020). Reconsidering the Role of Melatonin in Rheumatoid Arthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082877"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s00436-018-5860-4","article-title":"Human Colostrum Action against Giardia Lamblia Infection Influenced by Hormones and Advanced Maternal Age","volume":"117","author":"Pereira","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"521783","DOI":"10.1155\/2013\/521783","article-title":"The Angiotensin-Melatonin Axis","volume":"2013","author":"Campos","year":"2013","journal-title":"Int. J. Hypertens."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.febslet.2007.11.085","article-title":"Calmodulin Interacts with Angiotensin-Converting Enzyme-2 (ACE2) and Inhibits Shedding of Its Ectodomain","volume":"582","author":"Lambert","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0304-4165(96)00025-6","article-title":"In vitro Inhibition of Ca2+\/Calmodulin-Dependent Kinase II Activity by Melatonin","volume":"1290","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1096\/fasebj.12.13.1401","article-title":"Membrane-Bound Calmodulin in Xenopus Laevis Oocytes as a Novel Binding Site for Melatonin","volume":"12","author":"Romero","year":"1998","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3390\/v3060920","article-title":"Pattern Recognition Receptors and the Innate Immune Response to Viral Infection","volume":"3","author":"Thompson","year":"2011","journal-title":"Viruses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 Cytokine Storm; What We Know So Far","volume":"11","author":"Ragab","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1530\/JOE-12-0147","article-title":"Melatonin Inhibits IL1\u03b2-Induced MMP9 Expression and Activity in Human Umbilical Vein Endothelial Cells by Suppressing NF-\u039aB Activation","volume":"214","author":"Qin","year":"2012","journal-title":"J. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/j.1600-079X.2011.00950.x","article-title":"Melatonin Suppresses Acrolein-Induced IL-8 Production in Human Pulmonary Fibroblasts","volume":"52","author":"Kim","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2174\/1574887114666190528120357","article-title":"Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation","volume":"14","author":"Hameed","year":"2019","journal-title":"Rev. Recent Clin. Trials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"184.e9","DOI":"10.1016\/j.jcrc.2013.09.006","article-title":"Melatonin Suppresses Markers of Inflammation and Oxidative Damage in a Human Daytime Endotoxemia Model","volume":"29","author":"Alamili","year":"2014","journal-title":"J. Crit. Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.0902961","article-title":"Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation","volume":"184","author":"Weinlich","year":"2010","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1600-079X.2012.00982.x","article-title":"Melatonin Suppresses Proinflammatory Mediators in Lipopolysaccharide-Stimulated CRL1999 Cells via Targeting MAPK, NF-\u039aB, c\/EBP\u03b2, and P300 Signaling","volume":"53","author":"Shi","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12525","DOI":"10.1111\/jpi.12525","article-title":"Melatonin and Inflammation-Story of a Double-Edged Blade","volume":"65","author":"Hardeland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568026023394443","article-title":"Chemical and Physical Properties and Potential Mechanisms: Melatonin as a Broad Spectrum Antioxidant and Free Radical Scavenger","volume":"2","author":"Tan","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Rubio, M., Figueira, J.C., Acu\u00f1a-Castroviejo, D., Borobia, A.M., Escames, G., and de la Oliva, P. (2020). 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 Proto. Trials, 699.","DOI":"10.1186\/s13063-020-04632-4"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Galano, A., Tan, D.-X., and Reiter, R.J. (2018). Melatonin: A Versatile Protector against Oxidative DNA Damage. Molecules, 23.","DOI":"10.3390\/molecules23030530"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e12539","DOI":"10.1111\/jpi.12539","article-title":"Melatonin and Its Metabolites as Chemical Agents Capable of Directly Repairing Oxidized DNA","volume":"66","author":"Reiter","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1600-079X.2005.00265.x","article-title":"Beneficial Pleiotropic Actions of Melatonin in an Experimental Model of Septic Shock in Mice: Regulation of pro-\/Anti-Inflammatory Cytokine Network, Protection against Oxidative Damage and Anti-Apoptotic Effects","volume":"39","author":"Lardone","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/BF02849996","article-title":"Effects of Melatonin on Candida Sepsis in an Experimental Rat Model","volume":"24","author":"Yavuz","year":"2007","journal-title":"Adv. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109150","DOI":"10.1016\/j.biopha.2019.109150","article-title":"Protective Effects of Melatonin on Sepsis-Induced Liver Injury and Dysregulation of Gluconeogenesis in Rats through Activating SIRT1\/STAT3 Pathway","volume":"117","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Biancatelli, R.M.L.C., Berrill, M., Mohammed, Y.H., and Marik, P.E. (2020). Melatonin for the Treatment of Sepsis: The Scientific Rationale. J. Thorac. Dis., S54\u2013S65.","DOI":"10.21037\/jtd.2019.12.85"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/jpi.12134","article-title":"Melatonin as a Potential Therapy for Sepsis: A Phase I Dose Escalation Study and an Ex Vivo Whole Blood Model under Conditions of Sepsis","volume":"56","author":"Galley","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_61","first-page":"623","article-title":"Melatonin Restores the Mitochondrial Production of ATP in Septic Mice","volume":"27","author":"Escames","year":"2006","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1203\/00006450-200112000-00021","article-title":"Effects of Melatonin Treatment in Septic Newborns","volume":"50","author":"Gitto","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1096\/fj.02-0692fje","article-title":"Melatonin Counteracts Lipopolysaccharide-Induced Expression and Activity of Mitochondrial Nitric Oxide Synthase in Rats","volume":"17","author":"Escames","year":"2003","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/bja\/aer149","article-title":"Melatonin and Structurally Similar Compounds Have Differing Effects on Inflammation and Mitochondrial Function in Endothelial Cells under Conditions Mimicking Sepsis","volume":"107","author":"Lowes","year":"2011","journal-title":"Br. J. Anaesth."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2109","DOI":"10.1002\/rmv.2109","article-title":"Melatonin: Roles in Influenza, Covid-19, and Other Viral Infections","volume":"30","author":"Anderson","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, R., Wang, X., Ni, L., Di, X., Ma, B., Niu, S., Liu, C., and Reiter, R.J. (2020). COVID-19: Melatonin as a Potential Adjuvant Treatment. Life Sci.","DOI":"10.1016\/j.lfs.2020.117583"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s11481-020-09956-1","article-title":"Exogenous Melatonin as Potential Adjuvant in Anti-SarsCov2 Vaccines","volume":"15","author":"Maestroni","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1513\/AnnalsATS.201609-728PS","article-title":"Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship","volume":"14","author":"Lorente","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.jss.2016.05.020","article-title":"Melatonin: Is It an Effective Antioxidant for Pulmonary Contusion?","volume":"204","author":"Ozdinc","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/01902148.2013.866181","article-title":"Protective Effects of Melatonin and Quercetin on Experimental Lung Injury Induced by Carbon Tetrachloride in Rats","volume":"40","author":"Taslidere","year":"2014","journal-title":"Exp. Lung Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.transproceed.2012.01.097","article-title":"Protective Effect of Melatonin on Liver Ischemia-Reperfusion Induced Pulmonary Microvascular Injury in Rats","volume":"44","author":"Chiu","year":"2012","journal-title":"Transplant. Proc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7979","DOI":"10.3390\/ijms14047979","article-title":"Influence of Melatonin on the Immune System of Fish: A Review","volume":"14","author":"Esteban","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1600-079X.1999.tb00570.x","article-title":"Interactions of Melatonin with Membrane Models: Portioning of Melatonin in AOT and Lecithin Reversed Micelles","volume":"26","author":"Ceraulo","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/10715760290032593","article-title":"Effects of Antioxidants on Surfactant Peroxidation by Stimulated Human Polymorphonuclear Leukocytes","volume":"36","author":"Bouhafs","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Poissy, J., Goutay, J., Caplan, M., Parmentier, E., Duburcq, T., Lassalle, F., Jeanpierre, E., Rauch, A., Labreuche, J., and Susen, S. (2020). Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation, 184\u2013186.","DOI":"10.1161\/CIRCULATIONAHA.120.047430"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1600-079X.2007.00499.x","article-title":"Oral Melatonin Reduces Blood Coagulation Activity: A Placebo-Controlled Study in Healthy Young Men","volume":"44","author":"Wirtz","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Tobin, M.J., Jubran, A., and Laghi, F. (2021). Noninvasive Strategies in COVID-19: Epistemology, Randomised Trials, Guidelines, Physiology. Eur. Respir. J.","DOI":"10.1183\/13993003.04247-2020"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.arbres.2020.07.027","article-title":"Spontaneous Pneumothorax in COVID-19 Patients","volume":"57","author":"Marsico","year":"2021","journal-title":"Arch. Bronconeumol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Pedreira, P.R., Garc\u00eda-Prieto, E., Parra, D., Astudillo, A., Diaz, E., Taboada, F., and Albaiceta, G.M. (2008). Effects of Melatonin in an Experimental Model of Ventilator-Induced Lung Injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 295.","DOI":"10.1152\/ajplung.90211.2008"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/thoraxjnl-2020-216377","article-title":"Persistent Symptoms 1.5-6 Months after COVID-19 in Non-Hospitalized Subjects: A Population-Based Cohort Study","volume":"76","author":"Stavem","year":"2020","journal-title":"Thorax"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"m3026","DOI":"10.1136\/bmj.m3026","article-title":"Management of Post-Acute Covid-19 in Primary Care","volume":"370","author":"Greenhalgh","year":"2020","journal-title":"BMJ"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1136\/thoraxjnl-2020-215314","article-title":"Respiratory Follow-up of Patients with COVID-19 Pneumonia","volume":"75","author":"George","year":"2020","journal-title":"Thorax"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhao, X., Sun, J., Su, W., Shan, H., Zhang, B., Wang, Y., Shabanova, A., Shan, H., and Liang, H. (2018). Melatonin Protects against Lung Fibrosis by Regulating the Hippo\/YAP Pathway. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041118"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cell.2006.01.005","article-title":"From Cell Structure to Transcription: Hippo Forges a New Path","volume":"124","author":"Edgar","year":"2006","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1101\/gad.1602907","article-title":"Inactivation of YAP Oncoprotein by the Hippo Pathway Is Involved in Cell Contact Inhibition and Tissue Growth Control","volume":"21","author":"Zhao","year":"2007","journal-title":"Genes Dev."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Farhood, B., Aliasgharzadeh, A., Amini, P., Rezaeyan, A., Tavassoli, A., Motevaseli, E., Shabeeb, D., Musa, A.E., and Najafi, M. (2019). Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study. Medicina, 55.","DOI":"10.3390\/medicina55080417"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1139\/cjpp-2018-0529","article-title":"Melatonin Protects against COPD by Attenuating Apoptosis and Endoplasmic Reticulum Stress via Upregulating SIRT1 Expression in Rats","volume":"97","author":"He","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.intimp.2018.06.033","article-title":"Melatonin Attenuates Airway Inflammation via SIRT1 Dependent Inhibition of NLRP3 Inflammasome and IL-1\u03b2 in Rats with COPD","volume":"62","author":"Peng","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"95692","DOI":"10.18632\/oncotarget.21680","article-title":"Melatonin Suppresses Fibrotic Responses Induced by Cigarette Smoke via Downregulation of TGF-\u03921","volume":"8","author":"Shin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.lfs.2018.03.032","article-title":"Idiopathic Pulmonary Fibrosis (IPF) Signaling Pathways and Protective Roles of Melatonin","volume":"201","author":"Hosseinzadeh","year":"2018","journal-title":"Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00441-019-03148-x","article-title":"Melatonin Modulates Airway Smooth Muscle Cell Phenotype by Targeting the STAT3\/Akt\/GSK-3\u03b2 Pathway in Experimental Asthma","volume":"380","author":"Yu","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.imbio.2014.08.004","article-title":"Melatonin Reduces Airway Inflammation in Ovalbumin-Induced Asthma","volume":"219","author":"Shin","year":"2014","journal-title":"Immunobiology"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Artigas, L., Coma, M., Matos-Filipe, P., Aguirre-Plans, J., Farr\u00e9s, J., Valls, R., Fernandez-Fuentes, N., de la Haba-Rodriguez, J., Olvera, A., and Barbera, J. (2020). In-Silico Drug Repurposing Study Predicts the Combination of Pirfenidone and Melatonin as a Promising Candidate Therapy to Reduce SARS-CoV-2 Infection Progression and Respiratory Distress Caused by Cytokine Storm. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240149"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ramlall, V., Zucker, J., and Tatonetti, N. (2020). Melatonin Is Significantly Associated with Survival of Intubated COVID-19 Patients. medRxiv.","DOI":"10.1101\/2020.10.15.20213546"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"297","DOI":"10.32794\/mr11250063","article-title":"Melatonin as Adjuvant Treatment for Coronavirus Disease 2019 Pneumonia Patients Requiring Hospitalization (MAC-19 PRO): A Case Series","volume":"3","author":"Castillo","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ziaei, A., Davoodian, P., Dadvand, H., Safa, O., Hassanipour, S., Omidi, M., Masjedi, M., Mahmoudikia, F., Rafiee, B., and Fathalipour, M. (2020). Evaluation of the Efficacy and Safety of Melatonin in Moderately Ill Patients with COVID-19: A Structured Summary of a Study Protocol for a Randomized Controlled Trial. Trials, 882.","DOI":"10.1186\/s13063-020-04737-w"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:43:52Z","timestamp":1760165032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":96,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168623"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168623","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]}}}