{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:19:59Z","timestamp":1790194799117,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most studied rhinological disorders. Modifications of the respiratory nasal mucosa in COVID-19 patients are so far unknown. This paper presents a comparative morphological characterization of the respiratory nasal mucosa in CRSwNP versus COVID-19 and tissue interleukin (IL)-33 concentration. (2) Methods: We analyzed CRSwNP and COVID-19 samples through histopathology, scanning and transmission electron microscopy and performed proteomic determination of IL-33. (3) Results: Histopathologically, stromal edema (p &lt; 0.0001) and basal membrane thickening (p = 0.0768) were found more frequently in CRSwNP than in COVID-19. Inflammatory infiltrate was mainly eosinophil-dominant in CRSwNP and lymphocyte-dominant in COVID-19 (p = 0.3666). A viral cytopathic effect was identified in COVID-19. Scanning electron microscopy detected biofilms only in CRSwNP, while most COVID-19 samples showed microbial aggregates (p = 0.0148) and immune cells (p = 0.1452). Transmission electron microscopy of CRSwNP samples identified biofilms, mucous cell hyperplasia (p = 0.0011), eosinophils, fibrocytes, mastocytes, and collagen fibers. Extracellular suggestive structures for SARS-CoV-2 and multiple Golgi apparatus in epithelial cells were detected in COVID-19 samples. The tissue IL-33 concentration in CRSwNP (210.0 pg\/7 \u03bcg total protein) was higher than in COVID-19 (52.77 pg\/7 \u03bcg total protein) (p &lt; 0.0001), also suggesting a different inflammatory pattern. (4) Conclusions: The inflammatory pattern is different in each of these disorders. Results suggested the presence of nasal dysbiosis in both conditions, which could be a determining factor in CRSwNP and a secondary factor in COVID-19.<\/jats:p>","DOI":"10.3390\/jcm10184110","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"4110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Respiratory Nasal Mucosa in Chronic Rhinosinusitis with Nasal Polyps versus COVID-19: Histopathology, Electron Microscopy Analysis and Assessing of Tissue Interleukin-33"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-9474","authenticated-orcid":false,"given":"Ionu\u021b","family":"Jeican","sequence":"first","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"},{"name":"Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Gheban","sequence":"additional","affiliation":[{"name":"Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0360-016X","authenticated-orcid":false,"given":"Lucian","family":"Barbu-Tudoran","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory, 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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ini\u0219ca","sequence":"additional","affiliation":[{"name":"Department of Pathology, County Emergency Hospital, 330084 Deva, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Albu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania"},{"name":"Imogen Medical Research Institute, County Clinical Emergency Hospital, 400014 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-8926","authenticated-orcid":false,"given":"Maria","family":"Ilie\u0219","sequence":"additional","affiliation":[{"name":"Department of Proteomics and Metabolomics, MedFuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-8470","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0811-0821","authenticated-orcid":false,"given":"Mihaela","family":"Vic\u0103","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Institute of Legal Medicine, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horea","family":"Matei","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Institute of Legal Medicine, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Septimiu","family":"Tripon","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory, 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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Laz\u0103r","sequence":"additional","affiliation":[{"name":"Cantacuzino National Military-Medical Institute for Research and Development, 050096 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costel","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, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Clinical Hospital of Infectious Disease, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-312X","authenticated-orcid":false,"given":"Veronica","family":"Trombitas","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0345-0993","authenticated-orcid":false,"given":"Cristina","family":"Iuga","sequence":"additional","affiliation":[{"name":"Department of Proteomics and Metabolomics, MedFuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"},{"name":"Department of Pharmaceutical Analysis, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulian","family":"Opincariu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-7966","authenticated-orcid":false,"given":"Lia","family":"Junie","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41385-020-00359-2","article-title":"The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection","volume":"14","author":"Gallo","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1017\/S0022215111000016","article-title":"Biofilms in chronic rhinosinusitis: Systematic review and suggestions for future research","volume":"125","author":"Keir","year":"2011","journal-title":"J. Laryngol. Otol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1111\/all.14526","article-title":"Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation","volume":"75","author":"Hong","year":"2020","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European position paper on rhinosinusitis and nasal polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.anai.2019.12.001","article-title":"Biologics in chronic rhinosinusitis with nasal polyposis","volume":"124","author":"Laidlaw","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 5, 536\u2013544.","DOI":"10.1038\/s41564-020-0695-z"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.cell.2020.05.042","article-title":"SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract","volume":"182","author":"Hou","year":"2020","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/ACI.0000000000000602","article-title":"Systemic biomarkers of eosinophilic chronic rhinosinusitis","volume":"20","author":"Ho","year":"2020","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/imr.12619","article-title":"Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family","volume":"281","author":"Cayrol","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jaci.2017.07.051","article-title":"Chronic IL-33 expression predisposes to virus-induced asthma exacerbations by increasing type 2 inflammation and dampening antiviral immunity","volume":"141","author":"Werder","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/thoraxjnl-2016-208772","article-title":"The role of interleukin-33 in chronic rhinosinusitis","volume":"72","author":"Kim","year":"2017","journal-title":"Thorax"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e779","DOI":"10.1016\/S2665-9913(20)30340-4","article-title":"Imperfect storm: Is interleukin-33 the Achilles heel of COVID-19?","volume":"2","author":"Zizzo","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41423-021-00685-w","article-title":"IL-33 in COVID-19: Friend or foe?","volume":"18","author":"Liang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08923973.2020.1818770","article-title":"Future perspective: Biologic agents in patients with severe COVID-19","volume":"43","author":"Yalcin","year":"2021","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_15","unstructured":"WHO (2021, March 30). Infection Prevention and Control for the Safe Management of a Dead Body in the Context of COVID-19. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/331538\/WHO-COVID-19-lPC_DBMgmt-2020.1-eng.pdf."},{"key":"ref_16","unstructured":"(2021, March 30). Collection and Submission of Postmortem Specimens from Deceased Persons with Known or Suspected COVID-19, (Interim Guidance), Available online: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/hcp\/guidance-postmortem-specimens.html."},{"key":"ref_17","unstructured":"European Centre for Disease Prevention and Control (2021, March 30). Considerations Related to the Safe Handling of Bodies of Deceased Persons with Suspected or Confirmed COVID-19. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/considerations-related-safe-handling-bodies-deceased-persons-suspected-or."},{"key":"ref_18","unstructured":"(2021, March 30). National Institute for Public Health from Romania. Available online: https:\/\/www.cnscbt.ro\/index.php\/info-medical\/2047-metodologia-de-supraveghere-a-covid-19-actualizare-23-10-2020-1\/file."},{"key":"ref_19","first-page":"302","article-title":"Biofilm in nasal polyps","volume":"46","author":"Mladina","year":"2008","journal-title":"Rhinology"},{"key":"ref_20","first-page":"1203","article-title":"Long-term results of nasal surgery: Comparison of mini-invasive turbinoplasty","volume":"34","author":"Cocuzza","year":"2020","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13601-020-00332-z","article-title":"Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma","volume":"10","author":"Wang","year":"2020","journal-title":"Clin. Transl. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4193\/Rhino15.271","article-title":"Cellular phenotyping of chronic rhinosinusitis with nasal polyps","volume":"54","author":"Lou","year":"2016","journal-title":"Rhinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1002\/alr.22214","article-title":"Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement","volume":"8","author":"Lou","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2332\/allergolint.10-RAI-0231","article-title":"Eosinophilic chronic rhinosinusitis in Japan","volume":"59","author":"Ishitoya","year":"2010","journal-title":"Allergol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/alr.22194","article-title":"High tissue eosinophilia as a marker to predict recurrence for eosinophilic chronic rhinosinusitis: A systematic review and meta-analysis","volume":"8","author":"McHugh","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_26","first-page":"501","article-title":"Relationship between histologic changes and inflammatory markers in chronic rhinosinusitis","volume":"14","author":"Pyo","year":"2021","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tu, Y., Liu, J., Li, T., Zhou, X., Tan, K.S., Ong, H.H., Sun, K., Ouyang, Y., Liang, X., and Ong, Y.K. (2021). Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps. Inflammation, 1\u201312.","DOI":"10.1007\/s10753-021-01471-6"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S143","DOI":"10.1513\/AnnalsATS.201802-128AW","article-title":"Airway Epithelial Differentiation and Mucociliary Clearance","volume":"15","author":"Whitsett","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"NP120","DOI":"10.1177\/0145561319862207","article-title":"Epithelial Squamous Metaplasia and Dysplasia in Inflammatory Nasal Polyps: An Observational Study","volume":"100","author":"Stoiljkov","year":"2021","journal-title":"Ear Nose Throat J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1177\/1945892420953960","article-title":"Blood Eosinophilic and Basophilic Trends in Recurring and Non-Recurring Eosinophilic Rhinosinusitis with Nasal Polyps","volume":"35","author":"Brescia","year":"2021","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1097\/CM9.0000000000000387","article-title":"Nasal cytology with emphasis on mast cells can improve the diagnosis and treatment of chronic rhinosinusitis","volume":"132","author":"Ren","year":"2019","journal-title":"Chin. Med. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4049\/jimmunol.198.Supp.145.9","article-title":"Unlocking mast cell diversity in human nasal polyps","volume":"198","author":"Dwyer","year":"2017","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.4049\/jimmunol.1500905","article-title":"Aspirin-Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway","volume":"195","author":"Liu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/alr.21021","article-title":"Increased percentage of mast cells within sinonasal mucosa of chronic rhinosinusitis with nasal polyp patients independent of atopy","volume":"2","author":"Shaw","year":"2012","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1177\/000348940811701207","article-title":"Damage to ciliated epithelium in chronic rhinosinusitis: What is the role of bacterial biofilms?","volume":"117","author":"Galli","year":"2008","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.3389\/fcell.2020.630340","article-title":"WDPCP Modulates Cilia Beating Through the MAPK\/ERK Pathway in Chronic Rhinosinusitis with Nasal Polyps","volume":"8","author":"Ma","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_37","first-page":"e563","article-title":"Letter to Editor: Oral lesions in a patient with Covid-19","volume":"25","author":"Soares","year":"2020","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13000-020-01017-8","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)\u2014Anatomic pathology perspective on current knowledge","volume":"15","author":"Mohanty","year":"2020","journal-title":"Diagn. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1053\/j.semdp.2017.06.005","article-title":"Histopathology of viral infections of the lung","volume":"34","author":"Pritt","year":"2017","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0140-6736(20)31305-2","article-title":"Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series","volume":"396","author":"Bradley","year":"2020","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3910","DOI":"10.1038\/s41467-020-17796-z","article-title":"Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells","volume":"11","author":"Zhu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1183\/09031936.01.00093001","article-title":"The effects of coronavirus on human nasal ciliated respiratory epithelium","volume":"18","author":"Chilvers","year":"2001","journal-title":"Eur. Respir. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1038\/s41467-020-19057-5","article-title":"SARS-CoV-2 viral load is associated with increased disease severity and mortality","volume":"11","author":"Fajnzylber","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1056\/NEJMc2001737","article-title":"SARS-CoV-2 viral load in upper respiratory specimens of infected patients","volume":"382","author":"Zou","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jeican, I.I., Alua\u0219, M., Laz\u0103r, M., Barbu-Tudoran, L., Gheban, D., Ini\u0219ca, P., Albu, C., Tripon, S., Albu, S., and Siserman, C. (2021). Evidence of SARS-CoV-2 Virus in the Middle Ear of Deceased COVID-19 Patients. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091535"},{"key":"ref_46","first-page":"2152656720911605","article-title":"The Microbiome of the Nose-Friend or Foe?","volume":"11","author":"Soares","year":"2020","journal-title":"Allergy Rhinol."},{"key":"ref_47","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"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41421-021-00257-2","article-title":"Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients","volume":"7","author":"Zhong","year":"2021","journal-title":"Cell Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1093\/infdis\/jiu326","article-title":"High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia","volume":"210","author":"Wolter","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Westblade, L.F., Simon, M.S., and Satlin, M.J. (2021). Bacterial coinfections in coronavirus disease 2019. Trends Microbiol.","DOI":"10.1016\/j.tim.2021.03.018"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmi.2020.09.025","article-title":"Understanding the role of bacterial and fungal infection in COVID-19","volume":"27","author":"Rawson","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/00016489.2015.1092169","article-title":"Bacterial biofilms in chronic rhinosinusitis; distribution and prevalence","volume":"136","author":"Danielsen","year":"2016","journal-title":"Acta Otolaryngol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.otohns.2008.02.002","article-title":"Biofilms with fungi in chronic rhinosinusitis","volume":"138","author":"Healy","year":"2008","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1177\/0194599811399536","article-title":"Biofilms in chronic rhinosinusitis with nasal polyps","volume":"144","author":"Bezerra","year":"2011","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.chemgeo.2018.09.016","article-title":"Advanced biofilm staining techniques for TEM and SEM in geomicrobiology: Implications for visualizing EPS architecture, mineral nucleation, and microfossil generation","volume":"498","author":"Cutcheon","year":"2018","journal-title":"Chem. Geol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Relucenti, M., Familiari, G., Donfrancesco, O., Taurino, M., Li, X., Chen, R., Artini, M., Papa, R., and Selan, L. (2021). Microscopy Methods for Biofilm Imaging: Focus on SEM and VP-SEM Pros and Cons. Biology, 10.","DOI":"10.3390\/biology10010051"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Achinas, S., Yska, S.K., Charalampogiannis, N., Krooneman, J., and Euverink, G.J.W. (2020). A Technological Understanding of Biofilm Detection Techniques: A Review. Materials, 13.","DOI":"10.3390\/ma13143147"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/00005537-200302000-00013","article-title":"\u2018Eosinophilic fungal rhinosinusitis\u2019: A common disorder in Europe?","volume":"113","author":"Braun","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00020840-200502000-00003","article-title":"New paradigm for the roles of fungi and eosinophils in chronic rhinosinusitis","volume":"13","author":"Sasama","year":"2005","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.sjbs.2020.03.012","article-title":"Isolation of ultrasmall (filterable) bacteria from patients suffering from ME, and patients and staff of a paediatric hospital","volume":"27","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tim.2011.03.002","article-title":"Can viruses form biofilms?","volume":"19","author":"Thoulouze","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.3389\/fmicb.2020.02041","article-title":"Microbial Biofilms: Human T-cell Leukemia Virus Type 1 First in Line for Viral Biofilm but Far Behind Bacterial Biofilms","volume":"11","author":"Maali","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.kint.2021.01.004","article-title":"Best practices for correctly identifying coronavirus by transmission electron microscopy","volume":"99","author":"Bullock","year":"2021","journal-title":"Kidney Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1016\/S0140-6736(20)32079-1","article-title":"Why misinterpretation of electron micrographs in SARS-CoV-2-infected tissue goes viral","volume":"396","author":"Dittmayer","year":"2020","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"P\u00e9rez, A., Torregrosa, I., D\u2019Marco, L., Juan, I., Terradez, L., Sol\u00eds, M.\u00c1., Moncho, F., Carda-Batalla, C., Forner, M.J., and Gorriz, J.L. (2021). IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection. Viruses, 13.","DOI":"10.3390\/v13040587"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41593-020-00758-5","article-title":"Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19","volume":"24","author":"Meinhardt","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Saraste, J., and Prydz, K. (2021). Assembly and Cellular Exit of Coronaviruses: Hijacking an Unconventional Secretory Pathway from the Pre-Golgi Intermediate Compartment via the Golgi Ribbon to the Extracellular Space. Cells, 10.","DOI":"10.3390\/cells10030503"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/ijos.2014.48","article-title":"The mucosal immune system in the oral cavity-an orchestra of T cell diversity","volume":"6","author":"Wu","year":"2014","journal-title":"Int. J. Oral Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1038\/emm.2014.16","article-title":"Mucosal dendritic cells shape mucosal immunity","volume":"46","author":"Chang","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1165\/rcmb.2002-0230OC","article-title":"Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes","volume":"30","author":"Jahnsen","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Campana, P., Parisi, V., Leosco, D., Bencivenga, D., Della Ragione, F., and Borriello, A. (2020). Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection. Cells, 9.","DOI":"10.3390\/cells9092046"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1186\/1556-276X-6-455","article-title":"Comparison of immature and mature bone marrow-derived dendritic cells by atomic force microscopy","volume":"6","author":"Xing","year":"2011","journal-title":"Nanoscale Res. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11230","DOI":"10.1039\/C9RA00818G","article-title":"Properties of immature and mature dendritic cells: Phenotype, morphology, phagocytosis, and migration","volume":"9","author":"Kim","year":"2019","journal-title":"RSC Adv."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4049\/jimmunol.175.2.855","article-title":"Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be rescued for full effector function","volume":"175","author":"Dumortier","year":"2005","journal-title":"J. Immunol."},{"key":"ref_77","unstructured":"Johnson, L.R. (2004). Lymphocytes. Encyclopedia of Gastroenterology, Elsevier."},{"key":"ref_78","unstructured":"Anaya, J.M., Shoenfeld, Y., and Rojas-Villarraga, A. (2021, March 30). Introduction to T and B lymphocytes, Autoimmunity: From Bench to Bedside, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK459471\/."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lin, W., Suo, Y., Deng, Y., Fan, Z., Zheng, Y., Wei, X., and Chu, Y. (2015). Morphological change of CD4(+) T cell during contact with DC modulates T-cell activation by accumulation of F-actin in the immunology synapse. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0108-x"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in health and disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cyto.2016.10.010","article-title":"Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells","volume":"90","author":"Ishinaga","year":"2017","journal-title":"Cytokine"},{"key":"ref_82","first-page":"1685","article-title":"Increased TSLP, IL-33, IL-25, IL-19, IL 21 and amphiregulin (AREG) levels in chronic rhinosinusitis with nasal polyp","volume":"276","author":"Dogan","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1159\/000484527","article-title":"IL-33 Expression in Chronic Rhinosinusitis with Nasal Polyps and Its Relationship with Clinical Severity","volume":"79","author":"Song","year":"2017","journal-title":"ORL"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Soyka, M.B., Holzmann, D., Basinski, T.M., Wawrzyniak, M., Bannert, C., B\u00fcrgler, S., Akkoc, T., Treis, A., R\u00fcckert, B., and Akdis, M. (2015). The Induction of IL-33 in the Sinus Epithelium and Its Influence on T-Helper Cell Responses. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123163"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Huang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41467-021-22449-w","article-title":"IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals","volume":"12","author":"Stanczak","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.2217\/bmm-2020-0410","article-title":"Serum-soluble ST2 as a novel biomarker reflecting inflammatory status and illness severity in patients with COVID-19","volume":"14","author":"Zeng","year":"2020","journal-title":"Biomark. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:14Z","timestamp":1760166074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/18\/4110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,12]]},"references-count":88,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["jcm10184110"],"URL":"https:\/\/doi.org\/10.3390\/jcm10184110","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,12]]}}}