{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:29:47Z","timestamp":1791365387380,"version":"4.3.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1R001440"],"award-info":[{"award-number":["TL1R001440"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006988","name":"John S. Dunn Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006988","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting billions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.<\/jats:p>","DOI":"10.1038\/s41598-021-04622-9","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T06:02:59Z","timestamp":1641967379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium"],"prefix":"10.1038","volume":"12","author":[{"given":"Rachel A.","family":"Reyna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Kishimoto-Urata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Urata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Makishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodan","family":"Paessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junki","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"4622_CR1","unstructured":"Engineering, T.C.f.S.S.a. COVID-19 Dashboard. 2021; Available from: https:\/\/coronavirus.jhu.edu\/map.html."},{"issue":"13","key":"4622_CR2","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","volume":"382","author":"Q Li","year":"2020","unstructured":"Li, Q. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl. J. Med. 382(13), 1199\u20131207 (2020).","journal-title":"N Engl. J. Med."},{"issue":"3","key":"4622_CR3","doi-asserted-by":"publisher","first-page":"302","DOI":"10.4193\/Rhin20.140","volume":"58","author":"F Heidari","year":"2020","unstructured":"Heidari, F. et al. Anosmia as a prominent symptom of COVID-19 infection. Rhinology 58(3), 302\u2013303 (2020).","journal-title":"Rhinology"},{"issue":"7809","key":"4622_CR4","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","volume":"581","author":"R Wolfel","year":"2020","unstructured":"Wolfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581(7809), 465\u2013469 (2020).","journal-title":"Nature"},{"issue":"20","key":"4622_CR5","doi-asserted-by":"publisher","first-page":"3180","DOI":"10.1021\/acschemneuro.0c00596","volume":"11","author":"R Butowt","year":"2020","unstructured":"Butowt, R., Bilinska, K. & Von Bartheld, C. S. Chemosensory dysfunction in COVID-19: integration of genetic and epidemiological data points to D614G spike protein variant as a contributing factor. ACS Chem. Neurosci. 11(20), 3180\u20133184 (2020).","journal-title":"ACS Chem. Neurosci."},{"issue":"15","key":"4622_CR6","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1093\/cid\/ciaa330","volume":"71","author":"A Giacomelli","year":"2020","unstructured":"Giacomelli, A. et al. Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study. Clin. Infect. Dis. 71(15), 889\u2013890 (2020).","journal-title":"Clin. Infect. Dis."},{"issue":"5","key":"4622_CR7","doi-asserted-by":"publisher","first-page":"102581","DOI":"10.1016\/j.amjoto.2020.102581","volume":"41","author":"X Meng","year":"2020","unstructured":"Meng, X. et al. COVID-19 and anosmia: a review based on up-to-date knowledge. Am. J. Otolaryngol. 41(5), 102581 (2020).","journal-title":"Am. J. Otolaryngol."},{"issue":"8","key":"4622_CR8","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","volume":"277","author":"JR Lechien","year":"2020","unstructured":"Lechien, J. R. et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur. Arch. Otorhinolaryngol. 277(8), 2251\u20132261 (2020).","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"4622_CR9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.12688\/f1000research.28393.1","volume":"10","author":"E Mutiawati","year":"2021","unstructured":"Mutiawati, E. et al. Anosmia and dysgeusia in SARS-CoV-2 infection: incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms\u2014a systematic review and meta-analysis. F1000Res 10, 40 (2021).","journal-title":"F1000Res"},{"issue":"19","key":"4622_CR10","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1021\/acschemneuro.0c00460","volume":"11","author":"CS von Bartheld","year":"2020","unstructured":"von Bartheld, C. S., Hagen, M. M. & Butowt, R. Prevalence of chemosensory dysfunction in COVID-19 patients: a systematic review and meta-analysis reveals significant ethnic differences. ACS Chem. Neurosci. 11(19), 2944\u20132961 (2020).","journal-title":"ACS Chem. Neurosci."},{"issue":"18","key":"4622_CR11","doi-asserted-by":"publisher","first-page":"e174","DOI":"10.3346\/jkms.2020.35.e174","volume":"35","author":"Y Lee","year":"2020","unstructured":"Lee, Y. et al. Prevalence and duration of acute loss of smell or taste in COVID-19 patients. J. Korean Med. Sci. 35(18), e174 (2020).","journal-title":"J. Korean Med. Sci."},{"issue":"9","key":"4622_CR12","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1016\/j.cmi.2020.05.026","volume":"26","author":"A Patel","year":"2020","unstructured":"Patel, A. et al. New-onset anosmia and ageusia in adult patients diagnosed with SARS-CoV-2 infection. Clin. Microbiol. Infect. 26(9), 1236\u20131241 (2020).","journal-title":"Clin. Microbiol. Infect."},{"issue":"9","key":"4622_CR13","first-page":"2428","volume":"71","author":"JF Chan","year":"2020","unstructured":"Chan, J. F. et al. Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in a golden syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. 71(9), 2428\u20132446 (2020).","journal-title":"Clin. Infect. Dis."},{"issue":"7818","key":"4622_CR14","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/s41586-020-2342-5","volume":"583","author":"SF Sia","year":"2020","unstructured":"Sia, S. F. et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 583(7818), 834\u2013838 (2020).","journal-title":"Nature"},{"issue":"28","key":"4622_CR15","doi-asserted-by":"crossref","first-page":"16587","DOI":"10.1073\/pnas.2009799117","volume":"117","author":"M Imai","year":"2020","unstructured":"Imai, M. et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development. Proc. Natl. Acad. Sci. U S A 117(28), 16587\u201316595 (2020).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"issue":"4","key":"4622_CR16","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1021\/acschemneuro.0c00649","volume":"12","author":"S Urata","year":"2021","unstructured":"Urata, S. et al. Regeneration profiles of olfactory epithelium after SARS-CoV-2 infection in golden syrian hamsters. ACS Chem. Neurosci. 12(4), 589\u2013595 (2021).","journal-title":"ACS Chem. Neurosci."},{"issue":"31","key":"4622_CR17","doi-asserted-by":"publisher","first-page":"eabc5801","DOI":"10.1126\/sciadv.abc5801","volume":"6","author":"DH Brann","year":"2020","unstructured":"Brann, D. H. et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci. Adv. 6(31), eabc5801.\nhttps:\/\/doi.org\/10.1126\/sciadv.abc5801 (2020).","journal-title":"Sci. Adv."},{"issue":"2","key":"4622_CR18","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0006-8993(78)90460-2","volume":"140","author":"JW Harding","year":"1978","unstructured":"Harding, J. W., Getchell, T. V. & Margolis, F. L. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology. Brain Res. 140(2), 271\u2013285 (1978).","journal-title":"Brain Res."},{"issue":"11","key":"4622_CR19","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1021\/acschemneuro.0c00210","volume":"11","author":"K Bilinska","year":"2020","unstructured":"Bilinska, K. et al. Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age. ACS Chem. Neurosci. 11(11), 1555\u20131562 (2020).","journal-title":"ACS Chem. Neurosci."},{"key":"4622_CR20","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.bbi.2020.06.032","volume":"89","author":"B Bryche","year":"2020","unstructured":"Bryche, B. et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav. Immun. 89, 579\u2013586 (2020).","journal-title":"Brain Behav. Immun."},{"issue":"6","key":"4622_CR21","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1177\/1073858420956905","volume":"27","author":"R Butowt","year":"2020","unstructured":"Butowt, R. & von Bartheld, C. S. Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection. Neuroscientist, 27(6), 582\u2013603 (2020).","journal-title":"Neuroscientist"},{"key":"4622_CR22","unstructured":"Yang, M., & Crawley, J.N., Simple behavioral assessment of mouse olfaction. Curr. Protoc. Neurosci., Chapter 8: p. Unit 8 24 (2009)."},{"issue":"3","key":"4622_CR23","first-page":"493","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed, L. J. & Meunch, H.\u00a0A simple method of estimating fifty per cent endpoints. Am. J. Hyg. 27(3), 493\u2013497 (1938).","journal-title":"Am. J. Hyg"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04622-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04622-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04622-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T15:47:12Z","timestamp":1669304832000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04622-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,12]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["4622"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-04622-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-841631\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,12]]},"assertion":[{"value":"23 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"628"}}