{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:09:43Z","timestamp":1787069383637,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"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. Med."],"abstract":"<jats:p>\n                    One of the most striking reported symptoms in CoViD-19 is loss of smell and taste. The frequency of these impairments and their specificity as a potential central nervous system function biomarker are of great interest as a diagnostic clue for CoViD-19 infection as opposed to other similar symptomatologic diseases and because of their implication in viral pathogenesis. Here severe CoViD-19 was investigated by comparing self-report vs. testing of smell and taste, thus the objective severity of olfactory impairment and their possible correlation with other symptoms. Because a significant discrepancy between smell and taste testing vs. self-report results (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) emerges in our result, we performed a statistical analysis highlighting disagreement among normosmia (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.05), hyposmia, severe hyposmia, and anosmia (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.001) and, in hypogeusia and severe hypogeusia, while no differences are observed in normogeusia and ageusia. Therefore, we analyzed the olfactory threshold by an objective test revealing the distribution of hyposmic (34%), severe hyposmic (48%), and anosmic (13%) patients in severe CoViD-19. In severe CoViD-19 patients, taste is lost in 4.3% of normosmic individuals, 31.9% of hyposmic individuals, 46.8% of severe hyposmic individuals, and 17% of anosmic individuals. Moreover, 95% of 100 CoViD-19 patients objectively tested were affected by smell dysfunction, while 47% were affected by taste dysfunction. Furthermore, analysis by objective testing also highlighted that the severity of smell dysfunction in CoViD-19 subjects did not correlate with age and sex. In conclusion, we report by objective testing that the majority of CoViD-19 patients report severe anosmia, that most of the subjects have olfactory impairment rather than taste impairment, and, finally, that the olfactory impairment correlate with symptom onset and hospitalization (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.05). Patients who exhibit severe olfactory impairment had been hospitalized for about a week from symptom onset; double time has taken place in subjects with normosmia. Our results may be limited by the relatively small number of study participants, but these suggest by objective testing that hyposmia, severe hyposmia, and anosmia may relate directly to infection severity and neurological damage. The smell test assessment could be a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions, further therapeutic approach, and evaluation of neurological damage.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2020.589409","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:20:15Z","timestamp":1606868415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":60,"title":["Smell and Taste in Severe CoViD-19: Self-Reported vs. Testing"],"prefix":"10.3389","volume":"7","author":[{"given":"Andrea","family":"Mazzatenta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampiero","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"D'Ardes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Marinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Porreca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cipollone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Vecchiet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Falcicchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Panichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Origlia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Di Giulio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"B1","volume-title":"Clinical Management of COVID-19","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/2020.02.07.20021154","article-title":"The novel coronavirus, 2019-nCoV, is highly contagious and more infectious than initially estimated","author":"Sanche","year":"2020","journal-title":"medRxiv [Preprint]"},{"key":"B4","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1177\/0145561320920762","article-title":"Clinical presentation of COVID-19: a systematic review focusing on upper airway symptoms","volume":"99","author":"Lovato","year":"2020","journal-title":"Ear Nose Throat J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/joim.13089","article-title":"Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019","volume":"288","author":"Lechien","year":"2020","journal-title":"J Intern Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1093\/aje\/kwh255","article-title":"Different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures","volume":"160","author":"Wallinga","year":"2004","journal-title":"Am J Epidemiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.2807\/1560-7917.ES.2020.25.4.2000058","article-title":"Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus","volume":"25","author":"Riou","year":"2020","journal-title":"Euro Surveill."},{"key":"B9","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3201\/eid2602.190697","article-title":"Middle east respiratory syndrome coronavirus transmission","volume":"26","author":"Killerby","year":"2020","journal-title":"Emerg Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"12658","DOI":"10.1128\/JVI.01542-10","article-title":"Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2","volume":"84","author":"Matsuyama","year":"2010","journal-title":"J Virol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1101\/2020.01.31.929042","article-title":"The novel coronavirus 2019. (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells","author":"Hoffmann","year":"2020","journal-title":"bioRxiv [Preprint]"},{"key":"B14","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s15010-015-0720-y","article-title":"Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus","volume":"43","author":"Arabi","year":"2015","journal-title":"Infection"},{"key":"B17","doi-asserted-by":"publisher","first-page":"227","DOI":"10.3988\/jcn.2017.13.3.227","article-title":"Neurological complications during treatment of Middle East respiratory syndrome","volume":"13","author":"Kim","year":"2017","journal-title":"J Clin Neurol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3201\/eid1002.030638","article-title":"Possible central nervous system infection by SARS coronavirus","volume":"10","author":"Lau","year":"2004","journal-title":"Emerg Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1001\/archneur.61.11.1669","article-title":"Neuromuscular disorders in severe acute respiratory syndrome","volume":"61","author":"Tsai","year":"2004","journal-title":"Arch Neurol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1086\/444461","article-title":"Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis","volume":"41","author":"Xu","year":"2005","journal-title":"Clin Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"6683","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":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/ana.25807","article-title":"COVID-19: a global threat to the nervous system","volume":"88","author":"Koralnik","year":"2020","journal-title":"Ann Neurol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"295298","DOI":"10.4193\/Rhin20.116","article-title":"Presentation of new onset anosmia during the COVID-19 pandemic","volume":"58","author":"Hopkins","year":"2020","journal-title":"Rhinology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/S1473-3099(20)30293-0","article-title":"Smell and taste dysfunction in patients with COVID-19","volume":"20","author":"Xydakis","year":"2020","journal-title":"Lancet Infect"},{"key":"B25","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1002\/alr.22579","article-title":"Association of chemosensory dysfunction and COVID- 19 in patients presenting with influenza- like symptoms","volume":"10","author":"Yan","year":"2020","journal-title":"Int Forum Allergy Rhinol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1002\/hed.26204","article-title":"Objective evaluation of anosmia and ageusia in COVID-19 patients: single-center experience on 72 cases","volume":"42","author":"Vaira","year":"2020","journal-title":"Head Neck"},{"key":"B27","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1002\/alr.22587","article-title":"Smell dysfunction: a biomarker for COVID-19","volume":"10","author":"Moein","year":"2020","journal-title":"Int Forum Allergy Rhinol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/ene.14359","article-title":"Acute onset smell and taste disorders in the context of Covid-19: a pilot multicenter PCR-based case-control study","volume":"22","author":"Beltran-Corbellini","year":"2020","journal-title":"Eur J Neurol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1007\/s00405-020-06024-5","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease","volume":"277","author":"Lechien","year":"2020","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1083\/jcb.27.2.263","article-title":"Renewal of cells within taste buds","volume":"27","author":"Beidler","year":"1965","journal-title":"J Cell Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF01206454","article-title":"Neurogenesis and neuron regeneration in the olfactory system of mammals. I morphological aspects of differentiation and structural organization of the olfactory sensory neurons","volume":"8","author":"Graziadei","year":"1979","journal-title":"J Neurocytol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1001\/jama.2020.6771","article-title":"Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection","volume":"323","author":"Spinato","year":"2020","journal-title":"JAMA"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/0194599820926473","article-title":"The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: a systematic review and meta-analysis","volume":"163","author":"Tong","year":"2020","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B34","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"},{"key":"B35","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature."},{"key":"B36","doi-asserted-by":"publisher","first-page":"7264","DOI":"10.1128\/JVI.00737-08","article-title":"Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2","volume":"82","author":"Netland","year":"2008","journal-title":"J Virol"},{"key":"B37","volume-title":"District Clinician Manual: Hospital Care for Adolescents and Adults","year":"2020"},{"key":"B38","unstructured":"WHOWHO Director-General's Remarks at the Media Briefing on 2019-nCoV2020"},{"key":"B39","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3390\/pathogens9080627","article-title":"Objective olfactory findings in hospitalized severe COVID-19 patients","volume":"31","author":"Lechien","year":"2020","journal-title":"Pathogens."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1093\/ndt\/12.10.2093","article-title":"Odour perception in chronic renal disease","volume":"12","author":"Griep","year":"1997","journal-title":"Nephrol Dial Transplant"},{"key":"B41","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s12882-019-1312-3","article-title":"Impact of salt taste dysfunction on interdialytic weight gain for hemodialysis patients; a cross-sectional study","volume":"20","author":"Tanaka","year":"2019","journal-title":"BMC Nephrol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"19193","DOI":"10.18632\/oncotarget.8393","article-title":"Olfactory phenotypic expression unveils human aging","volume":"7","author":"Mazzatenta","year":"2016","journal-title":"Oncotarget"},{"key":"B43","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1288\/00005537-198801000-00017","article-title":"Evaluation of olfactory dysfunction in the connecticut chemosensory clinical research center","volume":"98","author":"Cain","year":"1998","journal-title":"Laryngoscope"},{"key":"B44","first-page":"121","article-title":"The influence of hypotensive drugs on the taste sensitivity in patients with primary hypertension","volume":"60","author":"Suliburska","year":"2012","journal-title":"Acta Pol Pharm"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1007\/s00405-020-06069-6","article-title":"The role of self-reported smell and taste disorders in suspected COVID-19","volume":"277","author":"Printza","year":"2020","journal-title":"Eur Arch Otorhinolaryngol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3758\/BF03208363","article-title":"Tests of human olfactory function: principal components analysis suggests that most measure a common source of variance","volume":"56","author":"Doty","year":"1994","journal-title":"Percept Psychophys"},{"key":"B47","doi-asserted-by":"publisher","first-page":"P187","DOI":"10.1093\/geronb\/50B.4.P187","article-title":"Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity","volume":"50","author":"Nordin","year":"1995","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"B48","doi-asserted-by":"crossref","DOI":"10.1002\/9781118971758","volume-title":"Handbook of Olfaction and Gustation","author":"Doty","year":"2015"},{"key":"B49","first-page":"98","article-title":"Olfaction in rhinology \u2013 methods of assessing the sense of smell","volume":"44","author":"Simmen","year":"2006","journal-title":"Rhinology."},{"key":"B50","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1037\/a0018766","article-title":"Influence of smell loss on taste function","volume":"124","author":"Stinton","year":"2010","journal-title":"Behav Neurosci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1097\/MLG.0b013e318161e53a","article-title":"Accuracy of self-report in detecting taste dysfunction","volume":"118","author":"Soter","year":"2008","journal-title":"Laryngoscope."},{"key":"B52","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.fsc.2004.04.006","article-title":"Smell and taste disorders","volume":"12","author":"Wrobel","year":"2004","journal-title":"Facial Plast Surg Clin North Am."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.otc.2004.06.010","article-title":"Clinical assessment of patients with smell and taste disorders","volume":"37","author":"Wrobel","year":"2004","journal-title":"Otolaryngol Clin North Am."},{"key":"B54","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1177\/10454411980090030201","article-title":"Chemosensory function and dysfunction","volume":"9","author":"Spielman","year":"1998","journal-title":"Crit Rev Oral Biol Med"},{"key":"B55","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1749-6632.2009.04102.x","article-title":"Olfactory impairment in adults","volume":"1170","author":"Schubert","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1002\/alr.22655","article-title":"Psychophysical tests reveal impaired olfaction but preserved gustation in COVID-19 patients","volume":"10","author":"Hintschich","year":"2020","journal-title":"Int Forum Allergy Rhinol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/0006-8993(77)91032-0","article-title":"Odorant responses in taste neurons of the rat NTS","volume":"135","author":"Van Buskirk","year":"1977","journal-title":"Brain Res"},{"key":"B58","article-title":"Chapter 36. A proposed model of a flavor modality","volume-title":"The Neural Bases of Multisensory Processes","author":"Small","year":"2012"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6284","DOI":"10.1523\/JNEUROSCI.3526-14.2015","article-title":"Odor-taste convergence in the nucleus of the solitary tract of the awake freely licking rat","volume":"35","author":"Escanilla","year":"2015","journal-title":"J Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3109\/00016488809125116","article-title":"Assessment of patients with taste and smell disorders","volume":"458","author":"Smith","year":"1998","journal-title":"Acta Otolaryngol Suppl"},{"key":"B61","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1093\/chemse\/20.6.645","article-title":"A study of the test-retest reliability of ten olfactory tests","volume":"20","author":"Doty","year":"1995","journal-title":"Chem Senses"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/hed.26269","article-title":"Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study","volume":"42","author":"Vaira","year":"2020","journal-title":"Head Neck."},{"key":"B63","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/0028-3932(85)90067-3","article-title":"Sex differences in odor identification ability: a cross-cultural analysis","volume":"23","author":"Doty","year":"1985","journal-title":"Neuropsychologia"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2020.589409\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T12:25:42Z","timestamp":1606998342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2020.589409\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,2]]},"references-count":63,"alternative-id":["10.3389\/fmed.2020.589409"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2020.589409","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,2]]},"article-number":"589409"}}