{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:29Z","timestamp":1785430469022,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0529200"],"award-info":[{"award-number":["2024ZD0529200"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271278"],"award-info":[{"award-number":["82271278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82271278"],"award-info":[{"award-number":["82271278"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Outstanding Youth Project of Natural Science Foundation of Hubei province","award":["2023020601012303"],"award-info":[{"award-number":["2023020601012303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Olfactory dysfunction (OD) is a common sequela of SARS-CoV-2 infection, but its prevalence and associated factors beyond 2 years remain unclear. In this multicenter observational study, we assessed 155 recovered COVID-19 patients approximately three years after infection and included 170 age-matched healthy controls as a reference group. Demographic, clinical, psychological, and sleep-related data were collected through structured interviews. Olfactory function at the 3-year assessment was objectively evaluated using Toyota\u2013Takagi (T&amp;T) olfactometry. Paired baseline-to-follow-up T&amp;T data were available only for a small exploratory subgroup of nine patients and were analyzed descriptively. At follow-up, 7 of 155 recovered patients (4.5%) met our T&amp;T-based definition of persistent quantitative olfactory dysfunction, all of whom were older than 50 years. Emotional and sleep disturbances were also common, with descriptive trends toward higher frequencies among women and older individuals. Exploratory analyses suggested that insomnia (AIS &gt; 6; OR 5.35, 95% CI 1.07\u201326.60; p = 0.033) and anxiety (HAMA \u2265 7; OR 10.54, 95% CI 1.21\u201391.82; p = 0.04) were associated with persistent T&amp;T-defined quantitative OD, although the small number of outcome events limited statistical precision. These findings indicate that a small proportion of COVID-19 survivors have persistent objective OD 3 years after infection and that persistent OD is associated with anxiety and insomnia.<\/jats:p>","DOI":"10.3390\/pathogens15050541","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:07:26Z","timestamp":1779206846000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Persistent Olfactory Dysfunction Three Years After COVID-19: A Multicenter Observational Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-7597","authenticated-orcid":false,"given":"Xinyu","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Dong","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9127-436X","authenticated-orcid":false,"given":"Hanshu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiying","family":"Kuang","sequence":"additional","affiliation":[{"name":"Wuhan Red Cross Hospital, Wuhan 430015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-8241","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Mclean Hospital, Harvard Medical School, Belmont, MA 02478, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-0522","authenticated-orcid":false,"given":"Nian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41563-020-00906-z","article-title":"Diagnostics for SARS-CoV-2 Infections","volume":"20","author":"Kevadiya","year":"2021","journal-title":"Nat. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1001\/jama.2025.5646","article-title":"Immunogenicity and Safety of Influenza and COVID-19 Multicomponent Vaccine in Adults \u2265 50 Years","volume":"333","author":"Spergel","year":"2025","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/s41591-024-02987-8","article-title":"Three-Year Outcomes of Post-Acute Sequelae of COVID-19","volume":"30","author":"Cai","year":"2024","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/chemse\/bjt072","article-title":"Olfactory Disorders and Quality of Life\u2014An Updated Review","volume":"39","author":"Croy","year":"2014","journal-title":"Chem. Senses"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/coa.13484","article-title":"An Unmet Need: Patients with Smell and Taste Disorders","volume":"45","author":"Erskine","year":"2020","journal-title":"Clin. Otolaryngol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Haehner, A., Marquardt, B., Kardashi, R., de With, K., R\u00f6\u00dfler, S., Landis, B.N., Welge-Luessen, A., and Hummel, T. (2022). SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses. Life, 12.","DOI":"10.3390\/life12030461"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1177\/0194599820926464","article-title":"Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance","volume":"163","author":"Sedaghat","year":"2020","journal-title":"Otolaryngol.\u2013Head Neck Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00408-020-00408-4","article-title":"ACE2: The Major Cell Entry Receptor for SARS-CoV-2","volume":"198","author":"Scialo","year":"2020","journal-title":"Lung"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.abn7760","article-title":"SARS-CoV-2 Omicron Variant: Antibody Evasion and Cryo-EM Structure of Spike Protein-ACE2 Complex","volume":"375","author":"Mannar","year":"2022","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41586-022-04569-5","article-title":"SARS-CoV-2 Is Associated with Changes in Brain Structure in UK Biobank","volume":"604","author":"Douaud","year":"2022","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41531-017-0019-z","article-title":"Synergistic Effects of Influenza and 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Can Be Eliminated by the Use of Influenza Therapeutics: Experimental Evidence for the Multi-Hit Hypothesis","volume":"3","author":"Sadasivan","year":"2017","journal-title":"npj Park. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"bjac010","DOI":"10.1093\/chemse\/bjac010","article-title":"Persisting Chemosensory Impairments in 366 Healthcare Workers Following COVID-19: An 11-Month Follow-Up","volume":"47","author":"Bussiere","year":"2022","journal-title":"Chem. Senses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e054598","DOI":"10.1136\/bmjopen-2021-054598","article-title":"Prevalence of Olfactory Dysfunction and Quality of Life in Hospitalised Patients 1 Year after SARS-CoV-2 Infection: A Cohort Study","volume":"12","author":"Tan","year":"2022","journal-title":"BMJ Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/alr.22990","article-title":"Long-Term Olfactory Dysfunction in COVID-19 Patients: 18-Month Follow-up Study","volume":"12","author":"Ferreli","year":"2022","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103962","DOI":"10.1016\/j.amjoto.2023.103962","article-title":"Olfactory Dysfunction Incidence and Resolution amongst 608 Patients with COVID-19 Infection","volume":"44","author":"Wu","year":"2023","journal-title":"Am. J. Otolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2642510","DOI":"10.1080\/07853890.2026.2642510","article-title":"Management of Long COVID-19 in Children and Adolescents: From Diagnosis to Therapeutically Approaches","volume":"58","author":"Gheorghita","year":"2026","journal-title":"Ann. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1002\/lary.28964","article-title":"Mood, Anxiety and Olfactory Dysfunction in COVID-19: Evidence of Central Nervous System Involvement?","volume":"130","author":"Speth","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41577-019-0190-z","article-title":"Sleep and Inflammation: Partners in Sickness and in Health","volume":"19","author":"Irwin","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112936","DOI":"10.1016\/j.psychres.2020.112936","article-title":"Psychological Status of Medical Workforce during the COVID-19 Pandemic: A Cross-Sectional Study","volume":"288","author":"Lu","year":"2020","journal-title":"Psychiatry Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.sleep.2020.07.045","article-title":"Sleep Quality and Mental Health in the Context of COVID-19 Pandemic and Lockdown in Morocco","volume":"74","author":"Lamkaddem","year":"2020","journal-title":"Sleep Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.smrv.2015.01.009","article-title":"The Pittsburgh Sleep Quality Index as a Screening Tool for Sleep Dysfunction in Clinical and Non-Clinical Samples: A Systematic Review and Meta-Analysis","volume":"25","author":"Mollayeva","year":"2016","journal-title":"Sleep Med. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e465","DOI":"10.1097\/MD.0000000000000465","article-title":"Olfactory Function and Quality of Life Following Microscopic Endonasal Transsphenoidal Pituitary Surgery","volume":"94","author":"Wang","year":"2015","journal-title":"Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/alr.23053","article-title":"Association of Computed Tomography Scores to Psychophysical Measures of Olfaction: A Systematic Review and Meta-Analysis","volume":"13","author":"Chen","year":"2023","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/gerona\/glz265","article-title":"A Prospective Study on Risk Factors for Olfactory Dysfunction in Aging","volume":"75","author":"Palmquist","year":"2020","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/pcn.12277","article-title":"Possible Relation between Olfaction and Anxiety in Healthy Subjects","volume":"69","author":"Takahashi","year":"2015","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jad.2020.09.014","article-title":"The Psychological Burden of the COVID-19 Pandemic and Associated Lockdown Measures: Experience from 4000 Participants","volume":"277","author":"Burhamah","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.bbi.2025.05.001","article-title":"A Long-Term Mixed Eosinophilic and Neutrophilic Chronic Rhinosinusitis C57BL\/6 Mouse Model with Neuroinflammation, Olfactory Dysfunction and Anxiety-like Behaviors","volume":"128","author":"Zhang","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101416","DOI":"10.1016\/j.arr.2021.101416","article-title":"Olfactory Dysfunction in Aging and Neurodegenerative Diseases","volume":"70","author":"Dan","year":"2021","journal-title":"Ageing Res. Rev."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:25:52Z","timestamp":1779207952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["pathogens15050541"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15050541","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]}}}