{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:30:07Z","timestamp":1784100607976,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"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>Background\/Objectives: Olfactory dysfunction and dysgeusia are common neurosensory manifestations of Coronavirus Disease 2019 (COVID-19), affecting approximately 60% of patients. These symptoms have been mechanistically linked to receptors involved in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cell entry, including angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), furin, and neuropilin-1 (NRP1), which are highly expressed in the olfactory epithelium. Nevertheless, clinical evidence supporting a direct association between receptor expression and sensory impairment remains inconsistent. Methods: We conducted a multicenter, observational, cross-sectional study including 104 adults with polymerase chain reaction\u2013confirmed SARS-CoV-2 infection during the first and second pandemic waves. Approximately 75 days after diagnosis, nasal and\/or pharyngeal samples were obtained to quantify gene expression levels of ACE2, TMPRSS2, furin, and NRP1 using quantitative polymerase chain reaction. Olfactory dysfunction and dysgeusia were recorded as dichotomous variables. Logistic regression analyses were performed with adjustment for age, sex, and race, considering receptor expression as continuous variables and as tertiles. Missing data were addressed using multiple imputation methods. Results: Olfactory dysfunction was reported by 37.5% of participants, and dysgeusia by 36.5%. No statistically significant associations were observed between baseline expression levels of ACE2, TMPRSS2, furin, or NRP1 and the presence of olfactory dysfunction or dysgeusia in either adjusted continuous or categorical models. Although these associations did not reach statistical significance, higher ACE2 and furin expression showed a nonsignificant trend toward an increased probability of sensory alterations, whereas intermediate NRP1 levels were associated with lower disease severity. Conclusions: COVID-19-related olfactory dysfunction and dysgeusia do not appear to be directly determined by isolated baseline expression of SARS-CoV-2 entry receptors. These findings support a multifactorial and dynamic pathophysiological model involving temporal receptor regulation, inflammatory processes, and host-related factors, highlighting the need for longitudinal and interventional studies.<\/jats:p>","DOI":"10.3390\/jcm15041659","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:58:21Z","timestamp":1771837101000},"page":"1659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations Between Nasal Receptors and Olfactory Dysfunction and Dysgeusia in Coronavirus Disease 2019 (COVID-19)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3241-0050","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Piqueras-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"},{"name":"Department of Otolaryngology, Faculty of Medicine, Campus de Ciencias de la Salud, University of Murcia (UMU), 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-7624","authenticated-orcid":false,"given":"Jos\u00e9 Francisco","family":"L\u00f3pez-Gil","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Esp\u00edritu Santo, Samborond\u00f3n 092301, Ecuador"},{"name":"Faculty of Health Sciences, Universidad Aut\u00f3noma de Chile, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0166-7117","authenticated-orcid":false,"given":"Diego","family":"Hell\u00edn-Meseguer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"},{"name":"Department of Otolaryngology, Faculty of Medicine, Campus de Ciencias de la Salud, University of Murcia (UMU), 30100 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-5380","authenticated-orcid":false,"given":"Juan","family":"Cabezas-Herrera","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"},{"name":"Molecular Therapy and Biomarkers Research Group, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0392-7569","authenticated-orcid":false,"given":"Gin\u00e9s Francisco","family":"Blesa-Llaona","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"},{"name":"Department of Otolaryngology, Faculty of Medicine, Campus de Ciencias de la Salud, University of Murcia (UMU), 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Meseguer-Cabezas","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Bernal-Morell","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"},{"name":"Department of Internal Medicine, Section of Infectious Diseases, Reina Sof\u00eda University Hospital (HRSU), University of Murcia (UMU), 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-5893","authenticated-orcid":false,"given":"Alfredo","family":"Minguela-Puras","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"},{"name":"Immunology Service, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-6105","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"D\u00edaz-Manzano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Clinical Hospital (HCUVA), 30120 Murcia, Spain"},{"name":"Department of Otolaryngology, Faculty of Medicine, Campus de Ciencias de la Salud, University of Murcia (UMU), 30100 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e14578","DOI":"10.14814\/phy2.14578","article-title":"Olfactory and gustatory dysfunction in COVID-19 patients: A meta-analysis study","volume":"8","author":"Hajikhani","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study","volume":"277","author":"Lechien","year":"2020","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lechien, J.R., Ducarme, M., Place, S., Chiesa-Estomba, C.M., Khalife, M., De Riu, G., Vaira, L.A., de Terwangne, C., Machayekhi, S., and Marchant, A. (2020). Objective Olfactory Findings in Hospitalized Severe COVID-19 Patients. Pathogens, 9.","DOI":"10.22541\/au.159050282.23236007"},{"key":"ref_4","unstructured":"Santamar\u00eda-Gadea, A., Izquierdo-Dom\u00ednguez, A., Mullol, J., and Alobid, I. (2022). Disfunci\u00f3n Olfatoria en la COVID-19 Persistente, SEORL."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1038\/s41598-024-53919-y","article-title":"Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions","volume":"14","author":"Rogn","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1021\/acschemneuro.0c00460","article-title":"Prevalence of Chemosensory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis Reveals Significant Ethnic Differences","volume":"11","author":"Hagen","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.12688\/f1000research.28393.1","article-title":"Anosmia and dysgeusia in SARS-CoV-2 infection: Incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms-a systematic review and meta-analysis","volume":"10","author":"Mutiawati","year":"2021","journal-title":"F1000 Res."},{"key":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","unstructured":"Mayi, B.S., Leibowitz, J.A., Woods, A.T., Ammon, K.A., Liu, A.E., and Raja, A. (2021). The role of Neuropilin-1 in COVID-19. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009153"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.medcli.2020.06.006","article-title":"P\u00e9rdida del sentido del olfato durante la pandemia COVID-19","volume":"155","author":"Mullol","year":"2020","journal-title":"Med. Cl\u00ednica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s12105-020-01212-5","article-title":"ACE2 & TMPRSS2 Expressions in Head & Neck Tissues: A Systematic Review","volume":"15","author":"Lechien","year":"2020","journal-title":"Head Neck Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"672","DOI":"10.7326\/M20-2428","article-title":"Loss of Smell and Taste in 2013 European Patients with Mild to Moderate COVID-19","volume":"173","author":"Lechien","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1021\/acschemneuro.0c00210","article-title":"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","volume":"11","author":"Bilinska","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104941","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.104941","article-title":"Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights","volume":"29","author":"Divani","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40463-020-00423-8","article-title":"Early recovery following new onset anosmia during the COVID-19 pandemic-an observational cohort study","volume":"49","author":"Hopkins","year":"2020","journal-title":"J. Otolaryngol.-Head Neck Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1001\/jamaneurol.2020.2125","article-title":"Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia","volume":"77","author":"Politi","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.otorri.2012.01.010","article-title":"Estudio objetivo del olfato mediante resonancia magn\u00e9tica funcional","volume":"63","author":"Toledano","year":"2012","journal-title":"Acta Otorrinolaringol\u00f3gica Esp."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107871","DOI":"10.1016\/j.intimp.2021.107871","article-title":"Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial","volume":"98","author":"Kasiri","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","unstructured":"Sociedad Iberoamericana de Informaci\u00f3n Cient\u00edfica (2022, May 20). Corticoides Intranasales Para la Recuperaci\u00f3n del Sentido del Olfato en Pacientes Con COVID-19. Available online: https:\/\/www.siicsalud.com\/dato\/resiiccompleto.php\/165751."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/all.14453","article-title":"COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI\/ARIA Position Paper","volume":"76","author":"Pfaar","year":"2021","journal-title":"Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1111\/all.14302","article-title":"Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement","volume":"75","author":"Bousquet","year":"2020","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2001948","DOI":"10.1183\/13993003.01948-2020","article-title":"Elevated ACE2 expression in the olfactory neuroepithelium: Implications for anosmia and upper respiratory SARS-CoV-2 entry and replication","volume":"56","author":"Chen","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","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":"ref_25","doi-asserted-by":"crossref","first-page":"eabc5801","DOI":"10.1126\/sciadv.abc5801","article-title":"Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia","volume":"6","author":"Brann","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117107","DOI":"10.1016\/j.jns.2020.117107","article-title":"Smell dysfunction in COVID-19 patients: More than a yes-no question","volume":"418","author":"Lima","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/00016357.2020.1787505","article-title":"Sudden onset, acute loss of taste and smell in coronavirus disease 2019 (COVID-19): A systematic review","volume":"78","author":"Samaranayake","year":"2020","journal-title":"Acta Odontol. Scand."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1021\/acs.jmedchem.1c00518","article-title":"Why All the Fury over Furin?","volume":"65","author":"Osman","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eabc3582","DOI":"10.1126\/sciimmunol.abc3582","article-title":"TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes","volume":"5","author":"Zang","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/path.5471","article-title":"Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)","volume":"251","author":"Bourgonje","year":"2020","journal-title":"J. Pathol."},{"key":"ref_31","unstructured":"Sungnak, W., Huang, N., B\u00e9cavin, C., and Berg, M. (2020). HCA Lung Biological Network. SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways. arXiv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41368-020-0074-x","article-title":"High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa","volume":"12","author":"Xu","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Doyle, M.E., Appleton, A., Liu, Q.R., Yao, Q., Mazucanti, C.H., and Egan, J.M. (2021). Human Taste Cells Express ACE2: A Portal for SARS-CoV-2 Infection. bioRxiv.","DOI":"10.1101\/2021.04.21.440680"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1128\/JVI.02202-13","article-title":"TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein","volume":"88","author":"Heurich","year":"2014","journal-title":"J. Virol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T09:21:21Z","timestamp":1771838481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,22]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041659"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041659","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,22]]}}}