{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:19:19Z","timestamp":1788304759003,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Since the onset of the COVID-19 pandemic, chemosensory dysfunction (CD), including olfactory and taste quantitative dysfunction (OD\/TD), has emerged as a prevalent and early symptom in SARS-CoV-2-infected subjects. This study explores the prevalence, duration, and recovery trajectory of COVID-19-related olfactory dysfunction (C19OD), with a specific focus on the four-year follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a combination of psychophysical tests (Sniffin\u2019 sticks) and patient-reported outcome measures (sVAS and tVAS), 83 participants were prospectively evaluated for OD and parosmia. Factors influencing long-term olfactory recovery were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Baseline assessments revealed OD in 56.6% of patients, with progressive improvement observed over 4\u202fyears. At the four-year follow-up, 92.3% of patients recovered their olfaction while the remaining still reported hyposmia. Younger age and olfactory training were found to be favourable prognostic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings show that, despite most individuals with C19OD recover olfaction within the first year, a subset of them continue to experience prolonged CD, demonstrating a slow, constant and meaningful improvement over years. This prolonged recovery period highlights the complexity of SARS-CoV-2\u2019s impact on olfactory function and highlights the need of further research on CD pathophysiology with the aim to improve therapeutic approaches to C19OD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncir.2025.1538821","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T05:13:46Z","timestamp":1746594826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Long-term self-reported symptoms and psychophysical tests in COVID-19 subjects experiencing persistent olfactory dysfunction: a 4-year follow-up study"],"prefix":"10.3389","volume":"19","author":[{"given":"Tommaso","family":"Saccardo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Roccuzzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonny","family":"Zampollo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Scarpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Nicolai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso Luca","family":"Pendolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Mucignat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Marchese-Ragona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Ottaviano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1080\/00016489.2022.2085326","article-title":"Olfactory function trends in COVID-19 patients: a prospective cohort study","volume":"142","author":"Akbari","year":"2022","journal-title":"Acta Otolaryngol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1002\/LIO2.507","article-title":"Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: an international survey","volume":"5","author":"Andrews","year":"2020","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1002\/alr.22828","article-title":"Comparison of self-reported symptoms and psychophysical tests in coronavirus disease 2019 (COVID-19) subjects experiencing long-term olfactory dysfunction: a 6-month follow-up study","volume":"11","author":"Bordin","year":"2021","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.4193\/RHIN24.233","article-title":"Adherence to olfactory training improves orthonasal and retronasal olfaction in post-COVID-19 olfactory loss","author":"Boscolo-Rizzo","year":"","journal-title":"Rhinology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1001\/jamaoto.2023.3603","article-title":"Olfactory and gustatory function 3 years after mild COVID-19\u2014a cohort psychophysical study","volume":"150","author":"Boscolo-Rizzo","year":"","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5625","DOI":"10.1007\/s00405-023-08227-y","article-title":"Evaluating long-term smell or taste dysfunction in mildly symptomatic COVID-19 patients: a 3-year follow-up study","volume":"280","author":"Boscolo-Rizzo","year":"","journal-title":"Eur. Arch. Otorrinolaringol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"103944","DOI":"10.1016\/j.amjoto.2023.103944","article-title":"Recovery from olfactory and gustatory dysfunction following COVID-19 acquired during omicron BA.1 wave in Italy","volume":"44","author":"Boscolo-Rizzo","year":"","journal-title":"Am. J. Otolaryngol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1097\/00005537-200404000-00026","article-title":"Prevalence of olfactory dysfunction: the Sk\u00f6vde population-based study","volume":"114","author":"Br\u00e4","year":"2004","journal-title":"Laryngoscope"},{"key":"ref001","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.tins.2022.11.003","article-title":"Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms","volume":"46","author":"Butowt","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jad.2013.12.026","article-title":"Olfaction as a marker for depression in humans","volume":"160","author":"Croy","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/wjo2.163","article-title":"Recovery rates and long-term olfactory dysfunction following COVID-19 infection","volume":"10","author":"Dias","year":"2024","journal-title":"World J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.molmed.2022.06.005","article-title":"Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health","volume":"28","author":"Doty","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1007\/s42399-021-00876-6","article-title":"Delayed parosmia following SARS-CoV-2 infection: a rare late complication of COVID-19","volume":"3","author":"Duyan","year":"2021","journal-title":"SN Compr. Clin. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.3390\/IJERPH19031036","article-title":"Olfactory dysfunction in COVID-19 patients who do not report olfactory symptoms: a pilot study with some suggestions for dentists","volume":"19","author":"Favero","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1093\/cid\/ciaa330\/5811989","article-title":"Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study","volume":"71","author":"Giacomelli","year":"2020","journal-title":"Clin Infect Dis"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.cmi.2020.05.017","article-title":"Anosmia in COVID-19 patients","volume":"26","author":"Hornuss","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1186\/s12967-023-04719-x","article-title":"Mechanism and treatment of olfactory dysfunction caused by coronavirus disease 2019","volume":"21","author":"Hu","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/S10863-018-9780-X","article-title":"Neural plasticity in developing and adult olfactory pathways\u2014focus on the human olfactory bulb","volume":"51","author":"Huart","year":"2019","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhino16.248","article-title":"Position paper on olfactory dysfunction","volume":"54","author":"Hummel","year":"2017","journal-title":"Rhinology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1177\/19458924221150977","article-title":"The efficacy of olfactory training as a treatment for olfactory disorders caused by coronavirus disease-2019: a systematic review and Meta-analysis","volume":"37","author":"Hwang","year":"2023","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/ohn.460","article-title":"Effectiveness of platelet-rich plasma for COVID-19-related olfactory dysfunction: a controlled study","volume":"170","author":"Lechien","year":"2024","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/S11882-022-01062-X","article-title":"Long-term consequences of COVID-19: chemosensory disorders","volume":"23","author":"Liao","year":"2023","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/lary.29277","article-title":"Parosmia is associated with relevant olfactory recovery after olfactory training","volume":"131","author":"Liu","year":"2021","journal-title":"Laryngoscope"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"241","DOI":"10.14639\/0392-100X-N0862","article-title":"Loss of smell in COVID-19 patients: a critical review with emphasis on the use of olfactory tests","volume":"40","author":"Marchese-Ragona","year":"2020","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1007\/s00405-022-07781-1","article-title":"Parosmia as a predictor of a better olfactory function in COVID-19: a multicentric longitudinal study for upper respiratory tract infections","volume":"280","author":"Menzel","year":"2023","journal-title":"Eur. Arch. Otorrinolaringol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1002\/lary.21387","article-title":"Health-related and specific olfaction-related quality of life in patients with chronic functional anosmia or severe hyposmia","volume":"121","author":"Neuland","year":"2011","journal-title":"Laryngoscope"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"CD013876","DOI":"10.1002\/14651858.CD013876.pub3","article-title":"Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction","volume":"2022","author":"O\u2019Byrne","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s00405-018-5248-1","article-title":"Updated Sniffin\u2019 sticks normative data based on an extended sample of 9139 subjects","volume":"276","author":"Oleszkiewicz","year":"2019","journal-title":"Eur. Arch. Otorrinolaringol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e111733","DOI":"10.1371\/journal.pone.0111733","article-title":"Sexual dimorphism in the human olfactory bulb: females have more neurons and glial cells than males","volume":"9","author":"Oliveira-Pinto","year":"2014","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"400","DOI":"10.4193\/Rhin20.136","article-title":"Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss","volume":"58","author":"Ottaviano","year":"2020","journal-title":"Rhinology"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"351","DOI":"10.4193\/Rhin17.152","article-title":"Influence of number of drugs on olfaction in the elderly","volume":"56","author":"Ottaviano","year":"2018","journal-title":"Rhinology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"157","DOI":"10.2500\/ajra.2013.27.3879","article-title":"Olfactory sensitivity and sexual desire in young adult and elderly men: an introductory investigation","volume":"27","author":"Ottaviano","year":"","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1007\/s00405-013-2441-0","article-title":"Human olfactory sensitivity for bourgeonal and male infertility: a preliminary investigation","volume":"270","author":"Ottaviano","year":"","journal-title":"Eur. Arch. Otorrinolaringol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1002\/LIO2.1160","article-title":"Clinical factors influencing olfactory performance in patients with persistent COVID-19 smell loss longer than 1 year","volume":"8","author":"Pendolino","year":"","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/ALR.23071","article-title":"Long-term quality-of-life impairment in patients with more than 1-year COVID-19-related olfactory dysfunction","volume":"13","author":"Pendolino","year":"","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"5152","DOI":"10.1038\/S41467-020-18963-Y","article-title":"Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness","volume":"11","author":"Pierron","year":"2020","journal-title":"Nat. Commun."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.1007\/s00405-021-07153-1","article-title":"Long-lasting olfactory dysfunction in COVID-19 patients","volume":"279","author":"Prem","year":"2022","journal-title":"Eur. Arch. Otorrinolaringol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/coa.14233","article-title":"Factors associated with persisting olfactory dysfunction after COVID-19","volume":"50","author":"Prem","year":"2024","journal-title":"Clin. Otolaryngol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/JCM10050966","article-title":"Smell and taste loss recovery time in COVID-19 patients and disease severity","volume":"10","author":"Printza","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/rhin19.410","article-title":"European position paper on diagnostic tools in rhinology","volume":"57","author":"Rimmer","year":"2019","journal-title":"Rhinology"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1017\/S0022215121002279","article-title":"Impact of olfactory dysfunction on quality of life in coronavirus disease 2019 patients: a systematic review","volume":"135","author":"Saniasiaya","year":"2021","journal-title":"J. Laryngol. Otol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"102889","DOI":"10.1016\/J.AMJOTO.2020.102889","article-title":"Onset and duration of symptoms of loss of smell\/taste in patients with COVID-19: a systematic review","volume":"42","author":"Santos","year":"2021","journal-title":"Am. J. Otolaryngol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e247818","DOI":"10.1001\/jamanetworkopen.2024.7818","article-title":"Long-term taste and smell outcomes after COVID-19","volume":"7","author":"Sharetts","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3389\/fpsyg.2019.00242","article-title":"Sex differences in human olfaction: a meta-analysis","volume":"10","author":"Sorokowski","year":"2019","journal-title":"Front. Psychol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1007\/S12070-021-02364-8","article-title":"Olfactory dysfunction in COVID-19 patients: findings from a tertiary rural centre","volume":"74","author":"Thakur","year":"2022","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3390\/life12020141","article-title":"The effects of persistent olfactory and gustatory dysfunctions on quality of life in long-COVID-19 patients","volume":"12","author":"Vaira","year":"2022","journal-title":"Life"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"32","DOI":"10.4193\/RHIN22.294","article-title":"Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study","volume":"61","author":"Vaira","year":"2023","journal-title":"Rhinology"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"E133","DOI":"10.1093\/CID\/CIAC613","article-title":"Omicron-associated changes in SARS-CoV-2 symptoms in the United Kingdom","volume":"76","author":"Vihta","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"3535","DOI":"10.1021\/acschemneuro.1c00542","article-title":"The D614G virus mutation enhances anosmia in COVID-19 patients: evidence from a systematic review and meta-analysis of studies from South Asia","volume":"12","author":"von Bartheld","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhino22.483","article-title":"Position paper on olfactory dysfunction: 2023 executive summary","volume":"61","author":"Whitcroft","year":"2023","journal-title":"Rhinology"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1001\/jama.2020.8391","article-title":"Olfactory dysfunction in COVID-19: diagnosis and management","volume":"323","author":"Whitcroft","year":"2020","journal-title":"JAMA"}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2025.1538821\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T05:13:47Z","timestamp":1746594827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2025.1538821\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":51,"alternative-id":["10.3389\/fncir.2025.1538821"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2025.1538821","relation":{},"ISSN":["1662-5110"],"issn-type":[{"value":"1662-5110","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]},"article-number":"1538821"}}