{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:56:52Z","timestamp":1776301012085,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>COVID-19-associated rhino-orbital mucormycosis has become a new clinical entity. This study\u2019s aim was to evaluate the histopathological and ultramicroscopic morphological aspects of this fungal infection. This was an observational retrospective study on eight patients from three tertiary centers in Romania. The tissue samples collected during functional endoscopic sinus surgery were studied through histopathological examination, scanning electron microscopy, and transmission electron microscopy. In the histopathological examination, the morphological aspects characteristic of mucormycosis in all cases were identified: wide aseptate hyphae with right-angle ramifications, which invade blood vessels. One case presented perineural invasion into the perineural lymphatics. And in another case, mucormycosis\u2013aspergillosis fungal coinfection was identified. Through scanning electron microscopy, long hyphae on the surface of the mucosa surrounded by cells belonging to the local immune system were identified in all samples, and bacterial biofilms were identified in half of the samples. Through transmission electron microscopy, aseptate hyphae and bacterial elements were identified in the majority of the samples. Rhino-orbital-cerebral mucormycosis associated with COVID-19 produces nasal sinus dysbiosis, which favors the appearance of bacterial biofilms. The way in which the infection develops depends on the interaction of the fungi with cells of the immune system.<\/jats:p>","DOI":"10.3390\/diagnostics14040429","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T08:29:37Z","timestamp":1707985777000},"page":"429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["COVID-19-Associated Rhino-Orbital Mucormycosis: Histological and Electron Microscopy Characteristics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-9474","authenticated-orcid":false,"given":"Ionu\u021b Isaia","family":"Jeican","sequence":"first","affiliation":[{"name":"Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-1263","authenticated-orcid":false,"given":"Delia Ioana","family":"Horhat","sequence":"additional","affiliation":[{"name":"Department of Ear-Nose-Throat, Victor Babes University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-2510","authenticated-orcid":false,"given":"Mihai","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Department of Ear-Nose-Throat, Carol Davila University of Medicine and Pharmacy, 050472 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-7626","authenticated-orcid":false,"given":"Adrian","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0360-016X","authenticated-orcid":false,"given":"Lucian","family":"Barbu-Tudoran","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory Prof. C. Cr\u0103ciun, Faculty of Biology and Geology, Babes-Bolyai University, 400006 Cluj-Napoca, Romania"},{"name":"Electron Microscopy Integrated Laboratory, National Institute for R&D of Isotopic and Molecular Technologies, 400293 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-5930","authenticated-orcid":false,"given":"Bogdan-Alexandru","family":"Gheban","sequence":"additional","affiliation":[{"name":"Department of Histology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Department of Pathology, Emergency Clinical County Hospital, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlad","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corneliu","family":"Toader","sequence":"additional","affiliation":[{"name":"Clinic of Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 041914 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-3758","authenticated-orcid":false,"given":"Maria","family":"Alua\u0219","sequence":"additional","affiliation":[{"name":"Department of Oral Health, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Costel Vasile","family":"Siserman","sequence":"additional","affiliation":[{"name":"Institute of Legal Medicine, 400006 Cluj-Napoca, Romania"},{"name":"Department of Legal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7755-4608","authenticated-orcid":false,"given":"Nicolae","family":"Balica","sequence":"additional","affiliation":[{"name":"Department of Ear-Nose-Throat, Victor Babes University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Vr\u00eenceanu","sequence":"additional","affiliation":[{"name":"Department of Ear-Nose-Throat, Carol Davila University of Medicine and Pharmacy, 050472 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silviu","family":"Albu","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery and Otorhinolaryngology, University Clinical Hospital of Railway Company, Iuliu Hatieganu University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.idc.2021.03.009","article-title":"Mucormycosis","volume":"35","author":"Steinbrink","year":"2021","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cmi.2018.07.011","article-title":"The epidemiology and clinical manifestations of mucormycosis: A systematic review and meta-analysis of case reports","volume":"25","author":"Jeong","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chopra, S., Setiya, S., Waknis, P.P., Kale, L., and Tidke, S. (2023). Various Treatment Modalities in COVID-19 Associated Facial Mucormycosis and the Need for its Surgical Management: A Systematic Review. J. Maxillofac. Oral. Surg., 1\u201322.","DOI":"10.1007\/s12663-023-01878-8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e789","DOI":"10.1002\/hsr2.789","article-title":"Comparative risk assessment of COVID-19 associated mucormycosis and aspergillosis: A systematic review","volume":"5","author":"Baral","year":"2022","journal-title":"Health Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.4103\/jfmpc.jfmpc_1307_21","article-title":"COVID-19 associated pulmonary mucormycosis: A systematic review of published cases with review of literature","volume":"11","author":"Rai","year":"2022","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Yasmin, F., Najeeb, H., Naeem, A., Dapke, K., Phadke, R., Asghar, M.S., Shah, S.M.I., De Berardis, D., and Ullah, I. (2021). COVID-19 Associated Mucormycosis: A Systematic Review from Diagnostic Challenges to Management. Diseases, 9.","DOI":"10.3390\/diseases9040065"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102146","DOI":"10.1016\/j.dsx.2021.05.019","article-title":"Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India","volume":"15","author":"Singh","year":"2021","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1007\/s12070-021-02638-1","article-title":"Mucormycosis of Paranasal Sinuses of Odontogenic Origin Post COVID19 Infection: A Case Series","volume":"74","author":"Saidha","year":"2022","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1007\/s12070-021-02825-0","article-title":"Risk Factors for Procurence of Mucormycosis and its Manifestations Post Covid-19: A Single Arm Retrospective Unicentric Clinical Study","volume":"74","author":"Gupta","year":"2022","journal-title":"Indian. J. Otolaryngol. Head. Neck Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20210648","DOI":"10.1259\/bjr.20210648","article-title":"Spectrum of MR imaging findings of sinonasal mucormycosis in post COVID-19 patients","volume":"94","author":"Kondapavuluri","year":"2021","journal-title":"Br. J. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/IOP.0000000000002030","article-title":"Clinical Presentations, Management and Outcomes of Rhino-Orbital-Cerebral Mucormycosis (ROCM) Following COVID-19: A Multi-Centric Study","volume":"37","author":"Dave","year":"2021","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.4103\/ijo.IJO_1565_21","article-title":"Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India\u2014Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1","volume":"69","author":"Sen","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.bjoms.2021.06.013","article-title":"COVID-19 associated mucormycosis (CAM) in India: A formidable challenge","volume":"59","author":"Rao","year":"2021","journal-title":"Br. J. Oral. Maxillofac. Surg."},{"key":"ref_14","unstructured":"Hern\u00e1ndez, J.L., and Buckley, C.J. (2023). StatPearls, StatPearls Publishing."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111643","DOI":"10.1016\/j.envres.2021.111643","article-title":"Mucormycosis: An opportunistic pathogen during COVID-19","volume":"201","author":"Mahalaxmi","year":"2021","journal-title":"Environ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1093\/cid\/cir868","article-title":"Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis)","volume":"54","author":"Walsh","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e403","DOI":"10.1016\/S1473-3099(17)30443-7","article-title":"Emerging issues, challenges, and changing epidemiology of fungal disease outbreaks","volume":"17","author":"Benedict","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Serris, A., Danion, F., and Lanternier, F. (2019). Disease Entities in Mucormycosis. J. Fungi, 5.","DOI":"10.3390\/jof5010023"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Morace, G., and Borghi, E. (2012). Invasive mold infections: Virulence and pathogenesis of mucorales. Int. J. Microbiol., 2012.","DOI":"10.1155\/2012\/349278"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Walther, G., Wagner, L., and Kurzai, O. (2019). Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa. J. Fungi, 5.","DOI":"10.3390\/jof5040106"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101401","DOI":"10.1016\/j.beha.2022.101401","article-title":"COVID-19 disease and immune dysregulation","volume":"35","author":"Davitt","year":"2022","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s43088-021-00165-0","article-title":"Corticosteroids for treatment of COVID-19: Effect, evidence, expectation and extent","volume":"10","author":"Patel","year":"2021","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/13693780500464930","article-title":"The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus","volume":"44","author":"Chakrabarti","year":"2006","journal-title":"Med. Mycol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101393","DOI":"10.1016\/j.mycmed.2023.101393","article-title":"COVID-19-associated mucormycosis in India: Why such an outbreak?","volume":"33","author":"Pasquier","year":"2023","journal-title":"J. Mycol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1016\/j.ajpath.2015.04.027","article-title":"Absence of Fungal Spore Internalization by Bronchial Epithelium in Mouse Models Evidenced by a New Bioimaging Approach and Transmission Electronic Microscopy","volume":"185","author":"Rammaert","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1002\/lio2.956","article-title":"Clinical and mycological investigations of post-COVID-19 acute invasive fungal sinusitis","volume":"7","author":"Eldsouky","year":"2022","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/S0140-6736(03)14904-5","article-title":"Glucocorticoids and invasive fungal infections","volume":"362","author":"Lionakis","year":"2003","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.3201\/eid2709.210934","article-title":"Multicenter Epidemiologic Study of Coronavirus Disease\u2013Associated Mucormycosis, India","volume":"27","author":"Patel","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_30","first-page":"504","article-title":"Mucormycosis in COVID-19: A systematic review of literature","volume":"29","author":"Nagalli","year":"2021","journal-title":"Infez. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3892\/etm.2021.10043","article-title":"Ultrasonography used in the diagnosis of chronic rhinosinusitis: From experimental imaging to clinical practice","volume":"21","author":"Neagos","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJM199707243370407","article-title":"Fungal sinusitis","volume":"337","author":"deShazo","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_33","unstructured":"Burkett, A., Saitornuang, S., and Leal, S.M. (2023, December 01). Zygomycetes. PathologyOutlines.com Website. Available online: https:\/\/www.pathologyoutlines.com\/topic\/microbiologyzygomycetes.html."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00405-008-0692-y","article-title":"Rhino-orbital-cerebral mucormycosis and aspergillosis: Differential diagnosis and treatment","volume":"266","author":"Arndt","year":"2009","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1128\/CMR.00053-10","article-title":"Histopathologic diagnosis of fungal infections in the 21st century","volume":"24","author":"Guarner","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e01022","DOI":"10.1016\/j.idcr.2020.e01022","article-title":"Cerebro-rhino-orbital mucormycosis and aspergillosis coinfection in a patient with diabetes mellitus: A case report","volume":"23","author":"Zayet","year":"2020","journal-title":"IDCases"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"486","DOI":"10.4103\/0975-2870.135278","article-title":"Rhino-oculo-cerebral aspergillus and mucor co-infections in an immunocompromised patient with type 2 diabetes mellitus","volume":"7","author":"Rit","year":"2014","journal-title":"Med. J. Dr. D.Y. Patil Univ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00428-004-1126-x","article-title":"Combined mucormycosis and aspergillosis of the oro-sinonasal region in a patient affected by Castleman disease","volume":"446","author":"Maiorano","year":"2005","journal-title":"Virchows Arch."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1002\/lary.29632","article-title":"Invasive Fungal Sinusitis in Post COVID-19 Patients: A New Clinical Entity","volume":"131","author":"Khafagy","year":"2021","journal-title":"Laryngoscope"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"375","DOI":"10.5858\/2001-125-0375-HFOZ","article-title":"Histologic features of zygomycosis: Emphasis on perineural invasion and fungal morphology","volume":"125","author":"Frater","year":"2001","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1177\/10668969221099626","article-title":"Histopathological Study of Mucormycosis in Post COVID-19 Patients and Factors Affecting it in a Tertiary Care Hospital","volume":"31","author":"Kumari","year":"2023","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/S0161-6420(97)30177-8","article-title":"Post-traumatic corneal mucormycosis caused by Absidia corymbifera","volume":"104","author":"Marshall","year":"1997","journal-title":"Ophthalmology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1046\/j.1439-0507.2002.00703.x","article-title":"Case report. Fatal rhinocerebral zygomycosis due to Rhizopus oryzae","volume":"45","author":"Romano","year":"2002","journal-title":"Mycoses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jdermsci.2005.01.010","article-title":"Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene","volume":"39","author":"Nagao","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jeican, I.I., Gheban, D., Barbu-Tudoran, L., Ini\u0219ca, P., Albu, C., Ilie\u0219, M., Albu, S., Vic\u0103, M.L., Matei, H.V., and Tripon, S. (2021). Respiratory Nasal Mucosa in Chronic Rhinosinusitis with Nasal Polyps versus COVID-19: Histopathology, Electron Microscopy Analysis and Assessing of Tissue Interleukin-33. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184110"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jeican, I.I., Barbu Tudoran, L., Florea, A., Flonta, M., Trombitas, V., Apostol, A., Dumitru, M., Alua\u0219, M., Junie, L.M., and Albu, S. (2020). Chronic Rhinosinusitis: MALDI-TOF Mass Spectrometry Microbiological Diagnosis and Electron Microscopy Analysis; Experience of the 2nd Otorhinolaryngology Clinic of Cluj-Napoca, Romania. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123973"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/4\/429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:00:13Z","timestamp":1760104813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/4\/429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["diagnostics14040429"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14040429","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]}}}