Association of chemosensory dysfunction and COVID‐19 in patients presenting with influenza‐like symptoms
Open accessAbstract
Background: Rapid spread of the severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID‐19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID‐19 may help facilitate screening and early isolation of cases. Methods: A single‐institution, cross‐sectional study evaluating patient‐reported symptoms with a focus on smell and taste was conducted using an internet‐based platform on adult subjects who underwent testing for COVID‐19. Logistic regression was employed to identify symptoms associated with COVID‐19 positivity. Results: A total of 1480 patients with influenza‐like symptoms underwent COVID‐19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID‐19–positive patients and 203 of 1378 (15%) COVID‐19–negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID‐19–positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID‐19–negative patients ( p < 0.001). Smell and taste impairment were independently and strongly associated with COVID‐19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08‐23.5; ageusia: aOR 10.2; 95% CI, 4.74‐22.1), whereas sore throat was associated with COVID‐19 negativity (aOR 0.23; 95% CI, 0.11‐0.50). Of patients who reported COVID‐19–associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness. Conclusion: In ambulatory individuals with influenza‐like symptoms, chemosensory dysfunction was strongly associated with COVID‐19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease‐related symptoms.
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A symptom more specific to COVID-19 infection is loss of taste and smell, in which loss of taste, or dysgeusia, occurs in approximately 88.8% of cases.
“a symptom more specific to COVID‐19 infection is loss of taste and smell, in which loss of taste, or dysgeusia, occurs in approximately 88.8% of cases.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [297]
Recovery from COVID-related anosmia often occurs over weeks.
“recovery from COVID-related anosmia often occurs over weeks (11, 17, 18)”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [18]
Dysfunction of smell in many COVID-19 patients is transient.
“Any reasonable pathophysiological mechanism for COVID-19-associated anosmia must account for the high penetrance of smell disorders relative to endemic viruses (12, 91, 92), the apparent suddenness of smell loss that can precede the development of other symptoms (11, 13), and the transient nature of dysfunction in many patients (11, 17, 18); definitive identification of the disease mechanisms”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [18]
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“001).(15) A research group in Milan showed that 34% of 59 SARS-CoV-2 positive hospitalized patients had smell and taste disorders.”
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“Notwithstanding, the prevalence of anosmia/hyposmia and ageusia/dysgeusia in that study was 68% and 71% respectively among COVID-19 patients, which overall was much more common than what we found in our study, probably due to the retrospective nature of our study (Yan et al. 2020).”
ResultPain Symptoms in Patients with Coronavirus Disease (COVID-19): A Literature Review
Weng, L., Su, X., & Wang, X. (2021) · Journal of Pain Research · doi:10.2147/jpr.s269206 · Cited by 141 · see citing works
Borsetto, D., Hopkins, C., Philips, V., Obholzer, R., Tirelli, G., Polesel, J., Calvanese, L., & Boscolo-Rizzo, P. (2020) · Rhinology · doi:10.4193/rhin20.185 · Cited by 138 · see citing works
“In addition, some authors speculate that paucisymptomatic patients may be affected by nasal-centric viral spread, whereas patients requiring hospitalization may be experiencing a more pulmonary-centric viral infection leading to increased rate of respiratory failure and need for hospitalization ((17)).”
BackgroundInfluentialChary, E., Carsuzaa, F., Trijolet, J.-P., Capitaine, A., Roncato-Sabéran, M., Fouet, K., Roblot, F., Catroux, M., Allix‐Béguec, C., & Dufour, X. (2020) · American Journal of Rhinology and Allergy · doi:10.1177/1945892420930954 · Cited by 133 · see citing works
“A statistically significant association between the olfactory and gustatory symptoms and the mildly symptomatic forms of the disease, which are mostly treated at home, was shown in the study by Yan et al.(17) Severe forms of Covid-19 requiring hospitalization were not associated with olfactory or gustatory disorders.”
BackgroundCNS implications of COVID-19: a comprehensive review
Nagu, P., Parashar, A., Behl, T., & Mehta, V. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0070 · Cited by 131 · see citing works
“These studies also highlighted the association of anosmiawith the taste disorder in these patients (Bagheri et al. 2020; Giacomelli et al. 2020; Menni et al. 2020; Spinato et al. 2020; Yan et al. 2020).”
BackgroundInfluentialSix-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19
Boscolo‐Rizzo, P., Menegaldo, A., Fabbris, C., Spinato, G., Borsetto, D., Vaira, L. A., Calvanese, L., Pettorelli, A., Sonego, M., Frezza, D., et al. (2021) · Chemical Senses · doi:10.1093/chemse/bjab006 · Cited by 129 · see citing works
Expression of ACE2 in Human Neurons Supports the Neuro-Invasive Potential of COVID-19 Virus
Xu, J., & Lazartigues, E. D. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00915-1 · Cited by 130 · see citing works
International consensus statement on allergy and rhinology: Olfaction
Patel, Z., Holbrook, E., Turner, J., Adappa, N., Albers, M. W., Altundağ, A., Appenzeller, S., Costanzo, R., Croy, I., Davis, G. E., et al. (2022) · International Forum of Allergy and Rhinology · doi:10.1002/alr.22929 · Cited by 119 · see citing works
Self-citationOlfactory and taste disorders in COVID-19: a systematic review
da Costa, K. V. T., Carnaúba, A. T. L., Rocha, K. W., de Andrade, K. C. L., Ferreira, S. M. S., & Menezes, P. D. L. (2020) · Brazilian Journal of Otorhinolaryngology · doi:10.1016/j.bjorl.2020.05.008 · Cited by 129 · see citing works
“In their first study, Yan et al.(15) evaluated 58 patients at the University of California San Diego Health hospital with positive laboratory tests for COVID-19 and 203 negative tests.”
InfluentialSmell and taste alterations in COVID‐19: a cross‐sectional analysis of different cohorts
Paderno, A., Schreiber, A., Grammatica, A., Raffetti, E., Tomasoni, M., Gualtieri, T., Taboni, S., Zorzi, S., Lombardi, D., Deganello, A., et al. (2020) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22610 · Cited by 127 · see citing works
SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods
Oliveira, B. A., de Oliveira, L. C., Sabino, É. C., & Okay, T. S. (2020) · Revista do Instituto de Medicina Tropical de São Paulo · doi:10.1590/s1678-9946202062044 · Cited by 128 · see citing works
Mutiawati, E., Fahriani, M., Mamada, S. S., Fajar, J. K., Frediansyah, A., Maliga, H. A., Ilmawan, M., Emran, T. B., Ophinni, Y., Ichsan, I., et al. (2021) · F1000Research · doi:10.12688/f1000research.28393.1 · Cited by 126 · see citing works
Boscolo‐Rizzo, P., Hummel, T. R., Hopkins, C. L., Dibattista, M., Menini, A., Spinato, G., Fabbris, C., Emanuelli, E., D’Alessandro, A., Marzolino, R., et al. (2021) · Rhinology Journal · doi:10.4193/rhin21.249 · Cited by 127 · see citing works
Central Nervous System Manifestations Associated with COVID-19
Divani, A. A., Andalib, S., Biller, J., Napoli, M. D., Moghimi, N., Rubiños, C., Nobleza, C. O., Sylaja, P. N., Toledano, M., Lattanzi, S., et al. (2020) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-020-01079-7 · Cited by 128 · see citing works
“In a case-control study of 1480 patients with influenza-like symptoms [56 • ], loss of smell and taste was observed in 68% and 71% of COVID-19 patients, respectively, and in 16% and 17% of COVID-19-negative patients, respectively.”
BackgroundInfluentialSix month follow-up of self-reported loss of smell during the COVID-19 pandemic
Hopkins, C. L., Šurda, P., Vaira, L. A., Lechien, J. R., Safarian, M., Saussez, S., & Kumar, N. (2020) · Rhinology Journal · doi:10.4193/rhin20.544 · Cited by 126 · see citing works
A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications
Roche, J. A., & Roche, R. (2020) · The FASEB Journal · doi:10.1096/fj.202000967 · Cited by 125 · see citing works
Olfactory Dysfunction: A Highly Prevalent Symptom of COVID‐19 With Public Health Significance
Sedaghat, A. R., Gengler, I. M., & Speth, M. M. (2020) · Otolaryngology · doi:10.1177/0194599820926464 · Cited by 123 · see citing works
Zhang, J., Lee, A. C.-Y., Chu, H., Chan, J. F., Fan, Z., Li, C., Liu, F., Chen, Y., Yuan, S., Poon, V. K., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa995 · Cited by 123 · see citing works
“Besides fever, upper and lower respiratory symptoms [6], olfactory dysfunction as manifested by partial or complete loss of olfactory function (hyposmia/anosmia), and dysgeusia have been frequently reported [7-11].”
BackgroundDysgeusia in COVID-19: Possible Mechanisms and Implications
Lozada-Nur, F., Chainani-Wu, N., Fortuna, G., & Sroussi, H. (2020) · Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2020.06.016 · Cited by 120 · see citing works
Neuropathology of COVID-19 (neuro-COVID): clinicopathological update
Lou, J. J., Movassaghi, M., Gordy, D. E., Olson, M. G., Zhang, T., Khurana, M. S., Chen, Z., Perez-Rosendahl, M. A., Thammachantha, S., Singer, E. J., et al. (2020) · Free Neuropathology · doi:10.17879/freeneuropathology-2021-2993 · Cited by 117 · see citing works
Sequelae in adults at 12 months after mild‐to‐moderate coronavirus disease 2019 (COVID‐19)
Boscolo‐Rizzo, P., Guida, F., Polesel, J., Marcuzzo, A. V., Capriotti, V., D’Alessandro, A., Zanelli, E., Marzolino, R., Lazzarin, C., Antonucci, P., et al. (2021) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22832 · Cited by 116 · see citing works
Smell and taste symptom‐based predictive model for COVID‐19 diagnosis
Roland, L. T., Gurrola, J. G., Loftus, P. A., Cheung, S. W., & Chang, J. L. (2020) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22602 · Cited by 115 · see citing works
Barnawi, A., Chhikara, P., Tekchandani, R., Kumar, N., & Alzahrani, B. A. (2021) · Future Generation Computer Systems · doi:10.1016/j.future.2021.05.019 · Cited by 116 · see citing works
“Fever is the most frequent symptom in patients with COVID-19 virus [12].”
Smell and taste disorders during COVID ‐19 outbreak: Cross‐sectional study on 355 patients
Dell’Era, V., Farri, F., Garzaro, G., Gatto, M., Valletti, P. A., & Garzaro, M. (2020) · Head & Neck · doi:10.1002/hed.26288 · Cited by 108 · see citing works
“Over the last weeks, an increasing number of authors reported a high rate of olfactory and gustatory dysfunctions in COVID-19 patients, sometimes presenting as the first symptom.(4-14) The main goal of the present study was to evaluate the prevalence of smell/taste disorders in a large COVID-19 positive population, co…”
BackgroundInfluentialCauses of hypogeusia/hyposmia in SARS‐CoV2 infected patients
Finsterer, J., & Stöllberger, C. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25903 · Cited by 112 · see citing works
Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective
Cerón, J. M. C., Lamy, E., Martı́nez-Subiela, S., López‐Jornet, P., Silva, F. C. E., Eckersall, P. D., & Tvarijonaviciute, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051491 · Cited by 112 · see citing works
“In addition, one of the symptoms, referred by many patients, is the loss of sensory acuity, including smell and taste [2].”
BackgroundAnosmia and dysgeusia in COVID-19: A systematic review
Carrillo-Larco, R. M., & Altez-Fernandez, C. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.15917.1 · Cited by 111 · see citing works
Covid‐19 and oral diseases: Crosstalk, synergy or association?
Brandini, D. A., Takamiya, A. S., Thakkar, P., Schaller, S. J., Rahat, R., & Naqvi, A. R. (2021) · Reviews in Medical Virology · doi:10.1002/rmv.2226 · Cited by 115 · see citing works
Meini, S., Suardi, L., Busoni, M., Roberts, A. T., & Fortini, A. (2020) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-020-06102-8 · Cited by 110 · see citing works
Romoli, M., Jelčić, I., Bernard‐Valnet, R., Azorín, D. G., Mancinelli, L., Akhvlediani, T., Monaco, S., Taba, P., & Sellner, J. (2020) · European Journal of Neurology · doi:10.1111/ene.14382 · Cited by 111 · see citing works
Onset and duration of symptoms of loss of smell/taste in patients with COVID-19: A systematic review
Santos, R. E. A., da Silva, M. G., Silva, M. C. B. D. M., Barbosa, D. A. M., Gomes, A. L. D. V., Galindo, L. C. M., Aragão, R. D. S., & Ferraz‐Pereira, K. N. (2021) · American Journal of Otolaryngology · doi:10.1016/j.amjoto.2020.102889 · Cited by 109 · see citing works
“Regarding olfactory disorders alone, six studies found a prevalence of over 68% [10,12,16,17,25,27] and two found a prevalence of less than 7.”
BackgroundInfluentialSARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19
Maiese, A., Manetti, A. C., Bosetti, C., Duca, F. D., Russa, R. L., Frati, P., Paolo, M. D., Turillazzi, E., & Fineschi, V. (2021) · Brain Pathology · doi:10.1111/bpa.13013 · Cited by 104 · see citing works
“Gustatory and olfactory dysfunctions seem to be two of the most frequent neurological symptoms associated with COVID19, especially in Western countries (16,17); the prevalence of these manifestations varies according to different studies, from 6% in Eastern countries (18) to more than 70% and 85% in the United States…”
BackgroundSpeth, M. M., Singer‐Cornelius, T., Oberle, M., Gengler, I., Brockmeier, S. J., & Sedaghat, A. R. (2020) · The Laryngoscope · doi:10.1002/lary.28964 · Cited by 106 · see citing works
Incomplete and late recovery of sudden olfactory dysfunction in COVID-19
Kosugi, E. M., Lavinsky, J., Romano, F. R., Fornazieri, M. A., Matsumoto, G. R. L. L., Lessa, M. M., Piltcher, O. B., & Sant’Anna, G. D. (2020) · Brazilian Journal of Otorhinolaryngology · doi:10.1016/j.bjorl.2020.05.001 · Cited by 107 · see citing works
“7,8,11---13 the present study, positive-COVID-19 patients with sudden olfactory dysfunction had more general inflammatory symptoms (with coughing, headache and fever being the most common ones) than negative-COVID-19 patients (89.7% vs. 73.7%; p = 0.02*), corroborating the supposition that…”
InfluentialBoscolo-Rizzo, P., Tirelli, G., Meloni, P., Hopkins, C., Madeddu, G., Vito, A. D., Gardenal, N., Valentinotti, R., Tofanelli, M., Borsetto, D., et al. (2022) · medRxiv · doi:10.1002/alr.22995 · Cited by 81 · see citing works
Taste Changes (Dysgeusia) in COVID-19: A Systematic Review and Meta-analysis
Aziz, M., Perisetti, A., Lee‐Smith, W., Gajendran, M., Bansal, P., & Goyal, H. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.05.003 · Cited by 105 · see citing works
Chung, T. W., Sridhar, S., Zhang, J., Chan, K., Li, H., Wong, F. K.-C., Ng, M., Tsang, R. K., Lee, A. C.-Y., Fan, Z., et al. (2020) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaa199 · Cited by 105 · see citing works
“Yan et al [4] USA 59 Chemosensory dysfunction Questionnaire 40/59 (68%) 29/59 (49%) Pathology at the olfactory epithelium”
BackgroundAmdal, C. D., Pe, M. L., Falk, R. S., Piccinin, C., Bottomley, A., Arrarás, J. I., Darlington, A., Hofsø, K., Holzner, B., Jørgensen, N. M. H., et al. (2021) · Quality of Life Research · doi:10.1007/s11136-021-02908-z · Cited by 105 · see citing works
Cellular senescence as a potential mediator of COVID‐19 severity in the elderly
Nehme, J., Borghesan, M., Mackedenski, S., Bird, T. G., & Demaria, M. (2020) · Aging Cell · doi:10.1111/acel.13237 · Cited by 94 · see citing works
“Elderly patients with severe cases of COVID-19 are also more likely to experience a host of neurological symptoms, suggestive of central nervous system infection, including impaired consciousness and loss of smell (Mao et al., 2020; Yan et al., 2020).”
BackgroundAbdukahil, S. A., Abe, R., Abel, L., Absil, L., Acker, A. M., Adachi, S., Adam, E., Adrião, D., Ainscough, K. M., Hssain, A. A., et al. (2021) · Infection · doi:10.1007/s15010-021-01599-5 · Cited by 97 · see citing works
“Altered sense of taste and smell have since been found to be strongly associated with the disease [6, 7].”
BackgroundComparison of COVID-19 and influenza characteristics
Bai, Y., & Tao, X. (2021) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2000479 · Cited by 94 · see citing works
Olfactory Dysfunction in the COVID-19 Outbreak
Izquierdo-Domínguez, A., Rojas‐Lechuga, M. J., Mullol, J., & Alobid, I. (2020) · Journal of Investigational Allergology and Clinical Immunology · doi:10.18176/jiaci.0567 · Cited by 95 · see citing works
“Yan et al [56] included a total of 1480 patients from the USA with influenza-like symptoms who underwent COVID-19 testing.”
BackgroundA Framework for Biomarkers of COVID-19 Based on Coordination of Speech-Production Subsystems
Quatieri, T. F., Talkar, T., & Palmer, J. S. (2020) · IEEE Open Journal of Engineering in Medicine and Biology · doi:10.1109/ojemb.2020.2998051 · Cited by 94 · see citing works
“and smell [7], [8] which can have implications for muscular control and proprioceptive feedback, respectively, in speech production.”
Yao, Y., Wang, H., & Liu, Z. (2020) · Clinical & Experimental Allergy · doi:10.1111/cea.13746 · Cited by 92 · see citing works
Anosmia and dysgeusia associated with SARS-CoV-2 infection: an age-matched case–control study
Carignan, A., Valiquette, L., Grenier, C., Musonera, J. B., Nkengurutse, D., Marcil-Héguy, A., Vettese, K., Marcoux, D., Valiquette, C., Xiong, W. T., et al. (2020) · Canadian Medical Association Journal · doi:10.1503/cmaj.200869 · Cited by 93 · see citing works
Taste and Smell Impairment in COVID‐19: An AAO‐HNS Anosmia Reporting Tool‐Based Comparative Study
Sayın, İ., Yaşar, K. K., & Yazıcı, Z. M. (2020) · Otolaryngology · doi:10.1177/0194599820931820 · Cited by 90 · see citing works
Kanjanaumporn, J., Aeumjaturapat, S., Snidvongs, K., Seresirikachorn, K., & Chusakul, S. (2020) · Asian Pacific Journal of Allergy and Immunology · doi:10.12932/ap-030520-0826 · Cited by 91 · see citing works
- Authors
- Yan, C. H., Faraji, F., Prajapati, D. P., Boone, C. E., & DeConde, A. S.
- Affiliations
- UC San Diego Health System (US)
- Corresponding author
- Yan, Carol H.
- Venue
- International Forum of Allergy & Rhinology
- Publisher
- Wiley
- Published
- 2020-06
- Volume
- 10
- Issue
- 7
- Pages
- 806-813
- ISSN
- 2042-6976 (ISSN-L)
- 2042-6984
- PMC
- PMC7262089
- OpenAlex
- W3015631092
- Cited by
- 754
- References
- 13
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 19 · 2023: 60 · 2022: 94 · 2021: 248 · 2020: 317 · 2019: 2
- FWCI
- 63.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Forum of Allergy & Rhinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Center for Advancing Translational Sciences (UL1TR001442)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Dermatology › Dermatological and COVID-19 studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, anosmia, ageusia, chemosensory dysfunction, flu-like symptoms, subclinical symptoms, symptom screening, sore throat, symptom resolution, virus transmission, asymptomatic transmission, outpatients, patient-reported symptoms, COVID-19 testing, COVID-19 isolation, COVID-19 recovery
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Adolescent, Adult, Aged, Aged, 80 and over, Olfaction Disorders, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Pneumonia, Viral, Taste Disorders, Prevalence, Coronavirus Infections, Young Adult, Pandemics
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