COVID-19-associated anosmia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.
Synonyms and keywords:
Overview
Anosmia has been formally recognized as a characteristic symptom of COVID-19 infection, and may be the most common sign of infection due to this virus.[1]
The extent of potential olfactory dysfunction due to COVID-19 is still unclear.[2]
Historical Perspective
- COVID-19 (SARS-CoV-2) outbreak initiated in December, 2019 in Wuhan, Hubei Province, China.[2]
- In April 17, 2020 Moein et al. demostrated a pronounced relation of olfactory dysfunction in patients with COVID-19 infection.[3]
- In April 17, Shweta et al. used artificial intelligence with the most advanced deep neural networks technology at the time, and proved that there was a 28.6-fold probability of having anosmia in COVID-19-positive than those negative, and that anosmia/dysgeusia was one of the earliest signatures of COVID-19.[4][2]
- In April 22, 2020 a study made by Beltrán-Corbellini et al. proved that the incidence rate of anosmia was significantly higher in individuals with COVID-19 (39.2%) patients than those with influenza (12.5%).[5]
Classification
Pathophysiology
- The extent of potential olfactory dysfunction due to COVID-19 is still unclear.[2][6]
- The genome sequence of (COVID-19) SARS-CoV-2 is a 29,903 bp single-stranded RNA.[2][7]
- Pathogenicity, virology, and predilection for infection site are different for every virus. The main pathogenic site for COVID-19 is throat and nose.[8][2]
- Viral loads of COVID-19 are higher in the nasal cavity than any other site of infection (throat, lungs), both, in symptomatic and asymptomatic individuals.[9][2]
- The mechanism of central nervous system (CNS) invasion is unclear.[10]
- Due to the special anatomy of the olfactory system, COVID-19 virus may invade the central nervous system infections via the cribriform plate.[2][11]
- It is thought that Goblet cells and ciliated cells of the nasal mucosa may be the initial site of COVID-19 infection when transmission is through airway.[2][12]
- Studies suggest that viruses may propagate from the nasal cavity to the olfactory bulb through neuron-to-neuron axonal transport or passive diffusion of released viral particles.[10]
Causes
Human strains of coronavirus (HCoVs) can infect and spread through the olfactory bulb.[10][1]
Now in day, more than 200 types of viruses are identified to cause anosmia; coronavirus strains (7 of them) are responsable of 10-15% of the cases.[1][13][2]
Differentiating COVID-19-associated anosmia from other Diseases
Anosmia due to COVID-19 infection may present indenticaly as other anosmias from upper respiratory viral infections.
Epidemiology and Demographics
- Postviral anosmia constitutes 40% of all anosmia causes in adults.[1][14]
- Severe olfactory loss (complete anosmia) is estimated to have an estimated prevalence of around 5% in general population studies (independently of infection).[1][15]
- Further studies are requiered to establish the incidence of anosmia in COVID-19+ patients.[1]
- The prevalence of anosmia related to COVID-19 vary widely from one study to the other among several countries:[16]
| Date of publication | Country | Author | Number of patients | Prevalence |
|---|---|---|---|---|
| March 26, 2020 | Italy | Giacomelli et al.[17] | 59 | 33.9% |
| March 27, 2020 | Iran | Bagheri et al.[18] | 10,069 | 48.23% |
| April 1, 2020 | Italy | Vaira et al.[19] | 320 | 19.4% |
| April 6, 2020 | European countries | Lechien et al.[20] | 417 | 85.6% |
| April 7, 2020 | United Kingdom | Menni et al.[21] | 579 | 59.41% |
| April 12, 2020 | United States | Yan et al.[22] | 59 | 68% |
| April 16, 2020 | France | Klopfenstein et al.[23] | 47 | 47% |
| April 17, 2020 | Iran | Moein et al.[3] | 60 | 98.33% |
| April 22, 2020 | United Kingdom | Spinato et al.[24] | 202 | 64.4% |
| April 22, 2020 | Iran | Heidari et al.[25] | 23 | 69.57% |
| April 22, 2020 | Spain | Beltran-Corbellini et al.[26] | 79 | 31.65% |
| April 24, 2020 | United States | Yan et al.[27] | 169 | 75.7% |
| May 1, 2020 | Germany | Luers et al.[28] | 72 | 74% |
| May 1, 2020 | Italy | Vaira et al.[29] | 33 | 75.8% |
Risk Factors
- The most common identified risk factors for developing anosmia in patients with COVID-19 infection are:[1][30][31]
- Susceptibility to COVID-19 infection is influenced to some degree by the host genotype, making a 47-fold heritability for anosmia.[2][32]
Screening
- Several ENT societies in the United Kingdom and the United States, have advised to treat anosmia marker of SARS-CoV-2 infection.[33][34][35]
- The American Academy of Otolaryngology (AAO) proposed for anosmia, hyposmia, and dysgeusia to be added to the list of screening tools for COVID-19 in otherwise asymptomatic individuals.[35][33]
Natural History, Complications, and Prognosis
Anosmia related to COVID-19, typically has a duration of 8.96 days.[2][36]
Approximately 98% of patients with anosmia related to COVID-19 recover within 28 days.[2][36]
Diagnosis
Diagnostic Study of Choice
Olfactory function test (OFT) has been the study of choice for diagnosis of anosmia and olfactory dysfunction.[37][2][3][38]
In many studies, full olfactory function tests have been disregarded.[2]
History and Symptoms
- Approximately two thirds of confirmed COVID-19 infections presented anosmia and dysgeusia at some point of the disease.[39]
- Anosmia may occur suddenly as the only symptom of COVID-19 in approximately 16% of individuals.[1][40]
- In a study, 74.4% reported complete loss of smell.[1]
- Anosmia occurs more commonly after the onset of other symptoms. In a study involving 1325 participants with anosmia (with no confirmatory COVID-19 test), 13% reported anosmia before their onset, 38.4% at the same time, and in 48.6% after the onset of symptoms.[1]
- A study reports that anosmia typically developes after 4.4 days of COVID-19 infection.[36][2]
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography or Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Self-administered olfactory function tests can help the early detection of COVID-19 and isolation.[2][41]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Hopkins C, Surda P, Kumar N (June 2020). "Presentation of new onset anosmia during the COVID-19 pandemic". Rhinology. 58 (3): 295–298. doi:10.4193/Rhin20.116. PMID 32277751 Check
|pmid=value (help). - ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 Meng X, Deng Y, Dai Z, Meng Z (June 2020). "COVID-19 and anosmia: A review based on up-to-date knowledge". Am J Otolaryngol. 41 (5): 102581. doi:10.1016/j.amjoto.2020.102581. PMC 7265845 Check
|pmc=value (help). PMID 32563019 Check|pmid=value (help). - ↑ 3.0 3.1 3.2 Moein, Shima T.; Hashemian, Seyed MohammadReza; Mansourafshar, Babak; Khorram‐Tousi, Ali; Tabarsi, Payam; Doty, Richard L. (2020). "Smell dysfunction: a biomarker for COVID‐19". International Forum of Allergy & Rhinology. doi:10.1002/alr.22587. ISSN 2042-6976.
- ↑ "[2004.09338] Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis".
- ↑ Beltrán‐Corbellini, Á.; Chico‐García, J. L.; Martínez‐Poles, J.; Rodríguez‐Jorge, F.; Natera‐Villalba, E.; Gómez‐Corral, J.; Gómez‐López, A.; Monreal, E.; Parra‐Díaz, P.; Cortés‐Cuevas, J. L.; Galán, J. C.; Fragola‐Arnau, C.; Porta‐Etessam, J.; Masjuan, J.; Alonso‐Cánovas, A. (2020). "Acute‐onset smell and taste disorders in the context of COVID‐19: a pilot multicentre polymerase chain reaction based case–control study". European Journal of Neurology. doi:10.1111/ene.14273. ISSN 1351-5101.
- ↑ Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, Damm M, Frasnelli J, Gudziol H, Gupta N, Haehne A, Holbrook E, Hong SC, Hornung D, Hüttenbrink KB, Kamel R, Kobayashi M, Konstantinidis I, Landis BN, Leopold DA, Macchi A, Miwa T, Moesges R, Mullol J, Mueller CA, Ottaviano G, Passali GC, Philpott C, Pinto JM, Ramakrishnan VJ, Rombaux P, Roth Y, Schlosser RA, Shu B, Soler G, Stjärne P, Stuck BA, Vodicka J, Welge-Luessen A (March 2017). "Position paper on olfactory dysfunction". Rhinol. Suppl. 54 (26): 1–30. doi:10.4193/Rhino16.248. PMID 29528615.
- ↑ Baig AM, Khaleeq A, Ali U, Syeda H (April 2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chem Neurosci. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. PMC 7094171 Check
|pmc=value (help). PMID 32167747 Check|pmid=value (help). - ↑ Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba N, Schipper D, van Run P, Leijten L, Sikkema R, Verschoor E, Verstrepen B, Bogers W, Langermans J, Drosten C, Fentener van Vlissingen M, Fouchier R, de Swart R, Koopmans M, Haagmans BL (May 2020). "Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model". Science. 368 (6494): 1012–1015. doi:10.1126/science.abb7314. PMC 7164679 Check
|pmc=value (help). PMID 32303590 Check|pmid=value (help). Vancouver style error: initials (help) - ↑ Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, Xia J, Guo Q, Song T, He J, Yen HL, Peiris M, Wu J (March 2020). "SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients". N. Engl. J. Med. 382 (12): 1177–1179. doi:10.1056/NEJMc2001737. PMC 7121626 Check
|pmc=value (help). PMID 32074444 Check|pmid=value (help). - ↑ 10.0 10.1 10.2 Dubé M, Le Coupanec A, Wong A, Rini JM, Desforges M, Talbot PJ (September 2018). "Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43". J. Virol. 92 (17). doi:10.1128/JVI.00404-18. PMC 6096804. PMID 29925652. Vancouver style error: initials (help)
- ↑ Koyuncu OO, Hogue IB, Enquist LW (April 2013). "Virus infections in the nervous system". Cell Host Microbe. 13 (4): 379–93. doi:10.1016/j.chom.2013.03.010. PMC 3647473. PMID 23601101.
- ↑ Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, Talavera-López C, Maatz H, Reichart D, Sampaziotis F, Worlock KB, Yoshida M, Barnes JL (May 2020). "SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes". Nat. Med. 26 (5): 681–687. doi:10.1038/s41591-020-0868-6. PMID 32327758 Check
|pmid=value (help). - ↑ Eccles R (November 2005). "Understanding the symptoms of the common cold and influenza". Lancet Infect Dis. 5 (11): 718–25. doi:10.1016/S1473-3099(05)70270-X. PMC 7185637 Check
|pmc=value (help). PMID 16253889. - ↑ Zhu N, Zhang D, Wang W et al. A Novel Welge -Lussen A, Wolfensberger M. (2006). "Olfactory disorders following upper respiratory tract infections". Adv Otorhinolaryngol.
- ↑ Brämerson A, Johansson L, Ek L, Nordin S, Bende M (April 2004). "Prevalence of olfactory dysfunction: the skövde population-based study". Laryngoscope. 114 (4): 733–7. doi:10.1097/00005537-200404000-00026. PMID 15064632.
- ↑ Menni, Cristina; Valdes, Ana; Freydin, Maxim B; Ganesh, Sajaysurya; El-Sayed Moustafa, Julia; Visconti, Alessia; Hysi, Pirro; Bowyer, Ruth C E; Mangino, Massimo; Falchi, Mario; Wolf, Jonathan; Steves, Claire; Spector, Tim (2020). doi:10.1101/2020.04.05.20048421. Missing or empty
|title=(help) - ↑ Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M (March 2020). "Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study". Clin. Infect. Dis. doi:10.1093/cid/ciaa330. PMC 7184514 Check
|pmc=value (help). PMID 32215618 Check|pmid=value (help). - ↑ Bagheri, Seyed Hamid Reza; Asghari, Ali Mohammad; Farhadi, Mohammad; Shamshiri, Ahmad Reza; Kabir, Ali; Kamrava, Seyed Kamran; Jalessi, Maryam; Mohebbi, Alireza; Alizadeh, Rafieh; Honarmand, Ali Asghar; Ghalehbaghi, Babak; Salimi, Alireza (2020). doi:10.1101/2020.03.23.20041889. Missing or empty
|title=(help) - ↑ Vaira LA, Salzano G, Deiana G, De Riu G (July 2020). "Anosmia and Ageusia: Common Findings in COVID-19 Patients". Laryngoscope. 130 (7): 1787. doi:10.1002/lary.28692. PMC 7228304 Check
|pmc=value (help). PMID 32237238 Check|pmid=value (help). - ↑ Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S (April 2020). "Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study". Eur Arch Otorhinolaryngol. doi:10.1007/s00405-020-05965-1. PMC 7134551 Check
|pmc=value (help). PMID 32253535 Check|pmid=value (help). - ↑ Menni, Cristina; Valdes, Ana; Freydin, Maxim B; Ganesh, Sajaysurya; El-Sayed Moustafa, Julia; Visconti, Alessia; Hysi, Pirro; Bowyer, Ruth C E; Mangino, Massimo; Falchi, Mario; Wolf, Jonathan; Steves, Claire; Spector, Tim (2020). doi:10.1101/2020.04.05.20048421. Missing or empty
|title=(help) - ↑ Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS (April 2020). "Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms". Int Forum Allergy Rhinol. doi:10.1002/alr.22579. PMC 7262089 Check
|pmc=value (help). PMID 32279441 Check|pmid=value (help). - ↑ Klopfenstein, T.; Kadiane-Oussou, N.J.; Toko, L.; Royer, P.-Y.; Lepiller, Q.; Gendrin, V.; Zayet, S. (2020). "Features of anosmia in COVID-19". Médecine et Maladies Infectieuses. doi:10.1016/j.medmal.2020.04.006. ISSN 0399-077X.
- ↑ Spinato, Giacomo; Fabbris, Cristoforo; Polesel, Jerry; Cazzador, Diego; Borsetto, Daniele; Hopkins, Claire; Boscolo-Rizzo, Paolo (2020). "Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection". JAMA. 323 (20): 2089. doi:10.1001/jama.2020.6771. ISSN 0098-7484.
- ↑ Heidari, F.; Karimi, E.; Firouzifar, M.; Khamushian, P.; Ansari, R.; Mohammadi Ardehali, M.; Heidari, F. (2020). "Anosmia as a Prominent Symptom of COVID-19 Infection". Rhinology journal. 58 (3): 302–303. doi:10.4193/Rhin20.140. ISSN 0300-0729.
- ↑ Beltrán‐Corbellini, Á.; Chico‐García, J. L.; Martínez‐Poles, J.; Rodríguez‐Jorge, F.; Natera‐Villalba, E.; Gómez‐Corral, J.; Gómez‐López, A.; Monreal, E.; Parra‐Díaz, P.; Cortés‐Cuevas, J. L.; Galán, J. C.; Fragola‐Arnau, C.; Porta‐Etessam, J.; Masjuan, J.; Alonso‐Cánovas, A. (2020). "Acute‐onset smell and taste disorders in the context of COVID‐19: a pilot multicentre polymerase chain reaction based case–control study". European Journal of Neurology. doi:10.1111/ene.14273. ISSN 1351-5101.
- ↑ Yan, Carol H.; Faraji, Farhoud; Prajapati, Divya P.; Ostrander, Benjamin T.; DeConde, Adam S. (2020). "Self‐reported olfactory loss associates with outpatient clinical course in COVID‐19". International Forum of Allergy & Rhinology. doi:10.1002/alr.22592. ISSN 2042-6976.
- ↑ Heindl, Ludwig M; Lehmann, Clara; Klein, Florian; Dewald, Felix; Augustin, Max; Wawer Matos, Philomena A; Loreck, Niklas; Rokohl, Alexander C; Luers, Jan C (2020). "Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19)". Clinical Infectious Diseases. doi:10.1093/cid/ciaa525. ISSN 1058-4838.
- ↑ Vaira, Luigi Angelo; Salzano, Giovanni; Petrocelli, Marzia; Deiana, Giovanna; Salzano, Francesco Antonio; De Riu, Giacomo (2020). "Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine". Head & Neck. doi:10.1002/hed.26228. ISSN 1043-3074.
- ↑ 30.0 30.1 Stogbauer J, Wirkner K, Engel C, Moebus S, Pundt N, Teismann H, Loffler M, Hummel T, Beule AG, Berger K (April 2020). "Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies". Rhinology. 58 (2): 184–191. doi:10.4193/Rhin19.181. PMID 31693018.
- ↑ 31.0 31.1 Wang X, Zhang C, Xia X, Yang Y, Zhou C (October 2019). "Effect of gender on odor identification at different life stages: a meta-analysis". Rhinology. 57 (5): 322–330. doi:10.4193/Rhin19.005. PMID 31152646.
- ↑ Williams, Frances MK; Freydin, Maxim; Mangino, Massimo; Couvreur, Simon; Visconti, Alessia; Bowyer, Ruth CE; Le Roy, Caroline I; Falchi, Mario; Sudre, Carole; Davies, Richard; Hammond, Christopher; Menni, Cristina; Steves, Claire; Spector, Tim (2020). doi:10.1101/2020.04.22.20072124. Missing or empty
|title=(help) - ↑ 33.0 33.1 Robert Pellegrin, Keiland W. Cooper, Antonella Di Pizio, Paule V. Joseph, Surabhi Bhutani, Valentina Parma (2020). "Corona Viruses and the Chemical Senses:
Past, Present, and Future". Oxford University. line feed character in
|title=at position 40 (help) - ↑ "www.entuk.org" (PDF).
- ↑ 35.0 35.1 "AAO-HNSF 2020 Annual Meeting & OTO Experience | American Academy of Otolaryngology-Head and Neck Surgery".
- ↑ 36.0 36.1 36.2 Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S (April 2020). "Features of anosmia in COVID-19". Med Mal Infect. doi:10.1016/j.medmal.2020.04.006. PMC 7162775 Check
|pmc=value (help). PMID 32305563 Check|pmid=value (help). - ↑ Ottaviano, G.; Carecchio, M.; Scarpa, B.; Marchese-Ragona, R. (2020). "Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss". Rhinology journal. 0 (0): 0–0. doi:10.4193/Rhin20.136. ISSN 0300-0729.
- ↑ Vaira, Luigi Angelo; Salzano, Giovanni; Petrocelli, Marzia; Deiana, Giovanna; Salzano, Francesco Antonio; De Riu, Giacomo (2020). "Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine". Head & Neck. doi:10.1002/hed.26228. ISSN 1043-3074.
- ↑ "Neue Corona-Symptome entdeckt: Virologe Hendrik Streeck zum Virus".
- ↑ Heidari F, Karimi E, Firouzifar M, Khamushian P, Ansari R, Mohammadi Ardehali M, Heidari F (June 2020). "Anosmia as a prominent symptom of COVID-19 infection". Rhinology. 58 (3): 302–303. doi:10.4193/Rhin20.140. PMID 32319971 Check
|pmid=value (help). - ↑ Vaira, Luigi Angelo; Salzano, Giovanni; Petrocelli, Marzia; Deiana, Giovanna; Salzano, Francesco Antonio; De Riu, Giacomo (2020). "Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine". Head & Neck. doi:10.1002/hed.26228. ISSN 1043-3074.