{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:58:25Z","timestamp":1790935105773,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Medical Hypotheses"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.mehy.2020.110455","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T11:24:47Z","timestamp":1607599487000},"page":"110455","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":28,"special_numbering":"C","title":["Methylene blue in covid-19"],"prefix":"10.1016","volume":"146","author":[{"given":"Giulio","family":"Scigliano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Augusto","family":"Scigliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mehy.2020.110455_b0005","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ijid.2020.04.057","article-title":"Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health","volume":"95","author":"Amirian","year":"2020","journal-title":"Int J Infectious Diseases"},{"key":"10.1016\/j.mehy.2020.110455_b0010","doi-asserted-by":"crossref","first-page":"104371","DOI":"10.1016\/j.jcv.2020.104371","article-title":"Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis","volume":"127","author":"Hu","year":"2020","journal-title":"J Clin Virol"},{"issue":"1","key":"10.1016\/j.mehy.2020.110455_b0015","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat Rev Dis Primers"},{"issue":"8","key":"10.1016\/j.mehy.2020.110455_b0020","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","article-title":"COVID-19 and Multiorgan Response","volume":"45","author":"Zaim","year":"2020","journal-title":"Curr Probl Cardiol"},{"key":"10.1016\/j.mehy.2020.110455_b0025","doi-asserted-by":"crossref","first-page":"105996","DOI":"10.1016\/j.rmed.2020.105996","article-title":"Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?","volume":"168","author":"Perrotta","year":"2020","journal-title":"Respir Med"},{"issue":"2","key":"10.1016\/j.mehy.2020.110455_b0030","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0035","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M20-2003","article-title":"Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study","volume":"173","author":"Wichmann","year":"2020","journal-title":"Ann Intern Med"},{"issue":"6","key":"10.1016\/j.mehy.2020.110455_b0040","doi-asserted-by":"crossref","DOI":"10.23736\/S0375-9393.20.14772-2","article-title":"First ultrastructural autoptic findings of SARS -Cov-2 in olfactory pathways and brainstem","volume":"86","author":"Bulfamante","year":"2020","journal-title":"Minerva Anestesiol"},{"issue":"2","key":"10.1016\/j.mehy.2020.110455_b0045","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J Pathol"},{"issue":"10234","key":"10.1016\/j.mehy.2020.110455_b0050","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"The Lancet"},{"issue":"1","key":"10.1016\/j.mehy.2020.110455_b0055","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1128\/MMBR.65.1.131-150.2001","article-title":"Molecular Pathways in Virus-Induced Cytokine Production","volume":"65","author":"Mogensen","year":"2001","journal-title":"Microbiol Mol Biol Rev"},{"issue":"5","key":"10.1016\/j.mehy.2020.110455_b0060","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41591-020-0869-5","article-title":"Temporal dynamics in viral shedding and transmissibility of COVID-19","volume":"26","author":"He","year":"2020","journal-title":"Nat Med"},{"issue":"6","key":"10.1016\/j.mehy.2020.110455_b0065","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S1473-3099(20)30200-0","article-title":"Clinical and virological data of the first cases of COVID-19 in Europe: a case series","volume":"20","author":"Lescure","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"10.1016\/j.mehy.2020.110455_b0070","doi-asserted-by":"crossref","first-page":"314S","DOI":"10.1378\/chest.122.6_suppl.314S","article-title":"Oxidant-Antioxidant Balance in Acute Lung Injury*","volume":"122","author":"Lang","year":"2002","journal-title":"Chest"},{"issue":"1","key":"10.1016\/j.mehy.2020.110455_b0075","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/00075198-200202000-00002","article-title":"Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome:","volume":"8","author":"Fink","year":"2002","journal-title":"Current Opinion in Critical Care"},{"issue":"6","key":"10.1016\/j.mehy.2020.110455_b0080","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1096\/fj.202000967","article-title":"A hypothesized role for dysregulated bradykinin signaling in COVID\u201019 respiratory complications","volume":"34","author":"Roche","year":"2020","journal-title":"FASEB j"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0085","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/15216540410001701642","article-title":"Oxygen Free Radicals and the Systemic Inflammatory Response","volume":"56","author":"Closa","year":"2004","journal-title":"IUBMB Life (International Union of Biochemistry and Molecular Biology: Life)"},{"issue":"10","key":"10.1016\/j.mehy.2020.110455_b0090","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1161\/01.ATV.20.10.2175","article-title":"Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology","volume":"20","author":"Griendling","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"10.1016\/j.mehy.2020.110455_b0095","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1006\/jsre.2000.6052","article-title":"Differential Upregulation of Cellular Adhesion Molecules at the Sites of Oxidative Stress in Experimental Acute Pancreatitis","volume":"96","author":"Telek","year":"2001","journal-title":"J Surg Res"},{"key":"10.1016\/j.mehy.2020.110455_b0100","doi-asserted-by":"crossref","first-page":"G1197","DOI":"10.1152\/ajpgi.2001.280.6.G1197","article-title":"Localized pancreatic NF-kappaB activation and inflammatory response in taurocholate-induced pancreatitis","volume":"280","author":"Vaquero","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"11","key":"10.1016\/j.mehy.2020.110455_b0105","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1139\/y82-201","article-title":"The pathophysiology of superoxide: roles in inflammation and ischemia","volume":"60","author":"McCord","year":"1982","journal-title":"Can J Physiol Pharmacol"},{"issue":"5","key":"10.1016\/j.mehy.2020.110455_b0110","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1084\/jem.170.5.1769","article-title":"Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells","volume":"170","author":"Curran","year":"1989","journal-title":"J Exp Med"},{"issue":"140\u2013141","key":"10.1016\/j.mehy.2020.110455_b0115","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0378-4274(02)00507-6","article-title":"Multiple pathways of peroxynitrite cytotoxicity","volume":"11","author":"Szab\u00f3","year":"2003","journal-title":"Toxicol Lett"},{"issue":"10","key":"10.1016\/j.mehy.2020.110455_b0120","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/S1473-3099(20)30434-5","article-title":"Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study","volume":"20","author":"Carsana","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"10.1016\/j.mehy.2020.110455_b0125","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1016\/0003-4975(93)91143-B","article-title":"Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure","volume":"56","author":"Casey","year":"1993","journal-title":"Ann Thoracic Surgery"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0130","doi-asserted-by":"crossref","first-page":"C719","DOI":"10.1152\/ajpcell.2001.280.4.C719","article-title":"Oxidant stress and endothelial cell dysfunction","volume":"280","author":"Lum","year":"2001","journal-title":"Am J Physiol-Cell Physiol"},{"issue":"1","key":"10.1016\/j.mehy.2020.110455_b0135","doi-asserted-by":"crossref","DOI":"10.1186\/s12872-015-0124-z","article-title":"Endothelial cell control of thrombosis","volume":"15","author":"Yau","year":"2015","journal-title":"BMC Cardiovasc Disord"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0140","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/bjd.19327","article-title":"SARS\u2010CoV\u20102 endothelial infection causes COVID\u201019 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases","volume":"183","author":"Colmenero","year":"2020","journal-title":"Br J Dermatol"},{"issue":"10","key":"10.1016\/j.mehy.2020.110455_b0145","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.dld.2020.05.030","article-title":"Intestinal ischemia in the COVID-19 era","volume":"52","author":"Norsa","year":"2020","journal-title":"Digestive Liver Disease"},{"issue":"15","key":"10.1016\/j.mehy.2020.110455_b0150","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.15420\/ecr.2020.22","article-title":"Myocardial and microvascular injury due to coronavirus disease 2019","volume":"23","author":"Montone","year":"2020","journal-title":"Eur Cardiol"},{"issue":"11","key":"10.1016\/j.mehy.2020.110455_b0155","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1007\/s00415-020-09990-2","article-title":"Neurological involvement of coronavirus disease 2019: a systematic review","volume":"267","author":"Ghannam","year":"2020","journal-title":"J Neurol"},{"key":"10.1016\/j.mehy.2020.110455_b0160","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/0378-4274(95)03532-X","article-title":"Toxicity of iron and hydrogen peroxide: the Fenton reaction","volume":"82-83","author":"Winterbourn","year":"1995","journal-title":"Toxicol Lett"},{"issue":"3","key":"10.1016\/j.mehy.2020.110455_b0165","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0006-2952(91)90311-R","article-title":"Methylene blue as an inhibitor of superoxide generation by xanthine oxidase","volume":"42","author":"Salaris","year":"1991","journal-title":"Biochem Pharmacol"},{"issue":"2","key":"10.1016\/j.mehy.2020.110455_b0170","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0006-2952(93)90072-5","article-title":"Inhibition of nitric oxide synthesis by methylene blue","volume":"45","author":"Mayer","year":"1993","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"10.1016\/j.mehy.2020.110455_b0175","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3892\/etm.2015.2349","article-title":"Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review","volume":"9","author":"Denny","year":"2015","journal-title":"Exp Ther Med"},{"key":"10.1016\/j.mehy.2020.110455_b0180","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jneuroim.2016.08.014","article-title":"Methylene blue alleviates experimental autoimmune encephalomyelitis by modulating AMPK\/SIRT1 signaling pathway and Th17\/Treg immune response","volume":"299","author":"Wang","year":"2016","journal-title":"J Neuroimmunol"},{"key":"10.1016\/j.mehy.2020.110455_b0185","doi-asserted-by":"crossref","unstructured":"Bojadzic D, Alcazar O, Buchwald P. Methylene Blue Inhibits In Vitro the SARS-CoV-2 Spike \u2013 ACE2 Protein-Protein Interaction \u2013 A Mechanism That Can Contribute to Its Antiviral Activity Against COVID-19. bioRxiv [Preprint] 2020 [cited 2020 October 21]. Available from https:\/\/doi.org\/10.1101\/2020.08.29.273441.","DOI":"10.1101\/2020.08.29.273441"},{"key":"10.1016\/j.mehy.2020.110455_b0190","doi-asserted-by":"crossref","unstructured":"Cagno V, MedagliaC, Cerny A, Cerny T , Tapparel C, Cerny E. Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro. bioRxiv [Preprint] 2020 [cited 2020 October 21]. Available fromhttps:\/\/doi.org\/10.1101\/2020.08.14.251090.","DOI":"10.1101\/2020.08.14.251090"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0195","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00045391-200307000-00009","article-title":"Methylene Blue:","volume":"10","author":"Clifton","year":"2003","journal-title":"Am J Ther"},{"issue":"6","key":"10.1016\/j.mehy.2020.110455_b0200","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/sj.bjp.0707430","article-title":"Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction","volume":"152","author":"Ramsay","year":"2007","journal-title":"Br J Pharmacol"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0205","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.niox.2010.01.006","article-title":"A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock","volume":"22","author":"Juffermans","year":"2010","journal-title":"Nitric Oxide"},{"issue":"3","key":"10.1016\/j.mehy.2020.110455_b0210","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.burns.2016.09.023","article-title":"Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy","volume":"43","author":"Prauchner","year":"2017","journal-title":"Burns"},{"issue":"4","key":"10.1016\/j.mehy.2020.110455_b0215","doi-asserted-by":"crossref","first-page":"e1030","DOI":"10.1542\/peds.2014-3722","article-title":"A Novel Use of Methylene Blue in the Pediatric ICU","volume":"136","author":"Rutledge","year":"2015","journal-title":"Pediatrics"},{"key":"10.1016\/j.mehy.2020.110455_b0220","doi-asserted-by":"crossref","first-page":"173494","DOI":"10.1016\/j.ejphar.2020.173494","article-title":"Application of methylene blue -vitamin C \u2013N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial","volume":"885","author":"Alamdari","year":"2020","journal-title":"Eur J Pharmacol"},{"issue":"12","key":"10.1016\/j.mehy.2020.110455_b0225","doi-asserted-by":"crossref","DOI":"10.1016\/j.neurobiolaging.2010.12.012","article-title":"Lest we forget you\u2013methylene blue","volume":"32","author":"Schirmer","year":"2011","journal-title":"Neurobiol Aging"},{"issue":"22","key":"10.1016\/j.mehy.2020.110455_b0230","first-page":"49","article-title":"On the value of methylene blue in malarial fever","volume":"2","author":"Thayer","year":"1892","journal-title":"Bull Johns Hopkins Hosp"}],"container-title":["Medical Hypotheses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987720333466?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306987720333466?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T19:21:18Z","timestamp":1759692078000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306987720333466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":46,"alternative-id":["S0306987720333466"],"URL":"https:\/\/doi.org\/10.1016\/j.mehy.2020.110455","relation":{},"ISSN":["0306-9877"],"issn-type":[{"value":"0306-9877","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Methylene blue in covid-19","name":"articletitle","label":"Article Title"},{"value":"Medical Hypotheses","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mehy.2020.110455","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"110455"}}