{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:09:51Z","timestamp":1780333791713,"version":"3.54.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000055","name":"national institute on deafness and other communication disorders","doi-asserted-by":"publisher","award":["DC000129"],"award-info":[{"award-number":["DC000129"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head and Neck Pathol"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.<\/jats:p>","DOI":"10.1007\/s12105-021-01378-6","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T16:02:33Z","timestamp":1630166553000},"page":"607-611","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Immunohistochemical and qPCR Detection of SARS-CoV-2 in the Human Middle Ear Versus the Nasal Cavity: Case Series"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5765-9496","authenticated-orcid":false,"given":"Arwa","family":"Kurabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang","family":"Pak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"DeConde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen F.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol H.","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"issue":"3","key":"1378_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102487","volume":"41","author":"V Fidan","year":"2020","unstructured":"Fidan V. New type of corona virus induced acute otitis media in adult. Am J Otolaryngol. 2020;41(3): 102487. https:\/\/doi.org\/10.1016\/j.amjoto.2020.102487.","journal-title":"Am J Otolaryngol"},{"issue":"7","key":"1378_CR2","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1080\/14992027.2020.1776406","volume":"59","author":"I Almufarrij","year":"2020","unstructured":"Almufarrij I, Uus K, Munro K. Does coronavirus affect the audio-vestibular system? A rapid systematic review. Int J of Audiol. 2020;59(7):487\u201391. https:\/\/doi.org\/10.1080\/14992027.2020.1776406.","journal-title":"Int J of Audiol"},{"issue":"12","key":"1378_CR3","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1080\/14992027.2020.1798519","volume":"59","author":"K Munro","year":"2020","unstructured":"Munro K, Uus K, Almufarrij I, Chaudhuri N, Yioe V. Persistent self-reported changes in hearing and tinnitus in post-hospitalisation COVID-19 cases. Int J of Audiol. 2020;59(12):889\u201390. https:\/\/doi.org\/10.1080\/14992027.2020.1798519.","journal-title":"Int J of Audiol"},{"issue":"3","key":"1378_CR4","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jinf.2012.12.002","volume":"66","author":"A Ruohola","year":"2013","unstructured":"Ruohola A, Pettigrew MM, Lindholm L, et al. Bacterial and viral interactions within the nasopharynx contribute to the risk of acute otitis media. J Infect. 2013;66(3):247\u201354. https:\/\/doi.org\/10.1016\/j.jinf.2012.12.002.","journal-title":"J Infect"},{"key":"1378_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1189\/jib.0709518","volume":"87","author":"LO Bakaletz","year":"2010","unstructured":"Bakaletz LO. Immunopathogenesis of polymicrobial otitis media. J Leukoc Biol. 2010;87:213\u201322. https:\/\/doi.org\/10.1189\/jib.0709518.","journal-title":"J Leukoc Biol"},{"key":"1378_CR6","doi-asserted-by":"publisher","unstructured":"Frazier KM, Hooper JE, Mostafa HH, Stewart CM. SARS-CoV-2 virus isolated from the mastoid and middle ear: implications for COVID-19 precautions during ear surgery [published correction appears in doi: https:\/\/doi.org\/10.1001\/jamaoto.2020.2950]. JAMA Otolaryngol Head Neck Surg 146(10):964\u2013966. https:\/\/doi.org\/10.1001\/jamaoto.2020.1922.","DOI":"10.1001\/jamaoto.2020.2950 10.1001\/jamaoto.2020.1922"},{"key":"1378_CR7","unstructured":"CDC website, Research use only 2019-novel coronavirus (2019-nCoV) real-time RT-PCR primers and probes, https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/lab\/rt-pcr-panel-primer-probes.html. Accessed March 12, 2020."},{"key":"1378_CR8","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s10096-020-04025-0","volume":"40","author":"FM Liotti","year":"2021","unstructured":"Liotti FM, Menchinelli G, Marchetti S, Morandotti GA, Sanguinetti M, Posteraro B, Cattani P. Evaluation of three commercial assays for SARS-CoV-2 molecular detection in upper respiratory tract samples. Eur J Clin Microbiol Infect Dis. 2021;40:269\u201377. https:\/\/doi.org\/10.1007\/s10096-020-04025-0.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"6518","key":"1378_CR9","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","volume":"370","author":"L Cantuti-Castelvetri","year":"2020","unstructured":"Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T, Levanov L, Szirovicza L, Tobi A, Kallio-Kokko H, \u00d6sterlund P, Joensuu M, Meunier FA, Butcher SJ, Winkler MS, Mollenhauer B, Helenius A, Gokce O, Teesalu T, Hepojoki J, Vapalahti O, Stadelmann C, Balistreri G, Simons M. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. 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Clin Infect Dis. 2014;59(3):376\u201383. https:\/\/doi.org\/10.1093\/cid\/ciu303.","journal-title":"Clin Infect Dis"},{"issue":"11","key":"1378_CR12","doi-asserted-by":"publisher","first-page":"3750","DOI":"10.1128\/JCM.01186-11","volume":"49","author":"MM Pettigrew","year":"2011","unstructured":"Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. J Clin Microbiol. 2011;49(11):3750\u20135. https:\/\/doi.org\/10.1128\/JCM.01186-11.","journal-title":"J Clin Microbiol"},{"issue":"6","key":"1378_CR13","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1086\/528685","volume":"46","author":"T Chonmaitree","year":"2008","unstructured":"Chonmaitree T, Revai K, Grady JJ, Clos A, Patel JA, Nair S, Fan J, Henrickson KJ. Viral upper respiratory tract infection and otitis media complication in young children. 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Rate of concurrent otitis media in upper respiratory tract infections with specific viruses. Arch Otolaryngol Head Neck Surg. 2009;135(1):17\u201321. https:\/\/doi.org\/10.1001\/archotol.135.1.17.","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"1378_CR16","first-page":"396","volume-title":"Ballenger's Otorhinolaryngology: Head and Neck Surgery","author":"JP Harris","year":"2002","unstructured":"Harris JP, Keithley EM, Gopen Q. Autoimmune ear disease and other autoimmune diseases with inner ear involvement. In: Snow JB, Ballenger JJ, editors. Ballenger\u2019s Otorhinolaryngology: Head and Neck Surgery. Ontario: Hamilton; 2002. p. 396\u2013407."}],"container-title":["Head and Neck Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-021-01378-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12105-021-01378-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-021-01378-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T16:45:55Z","timestamp":1654879555000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12105-021-01378-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["1378"],"URL":"https:\/\/doi.org\/10.1007\/s12105-021-01378-6","relation":{},"ISSN":["1936-0568"],"issn-type":[{"value":"1936-0568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]},"assertion":[{"value":"14 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Ryan is a co-founder of Otonomy Inc., serves as a member of the Scientific Advisory Board, and holds an equity position in the company. The UCSD Committee on Conflict of Interest has approved this relationship. Otonomy, Inc. played no part in the research reported here. The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Autopsy and use of human tissues was reviewed and approved by the Institutional Review Board of the University of California San Diego School of Medicine. (IRB#191951 & 151473).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Consent was obtained per IRB and no personal identifying data is shared in the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}