COVID-19-associated anosmia: Difference between revisions

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{{SI}}
{{SI}}


{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo M.D.]]
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo M.D.]] {{Fs}}


{{SK}}  
{{SK}} [[anosmia]], olfactory dysfunction, [[SARS-CoV-2]], [[dysgeusia]]


==Overview==
==Overview==
[[Anosmia]] has been formally recognized as a characteristic [[symptom]] of [[COVID-19]] [[infection]], and may be the most common [[Sign (medicine)|sign]] of [[infection]] due to this [[Virus (biology)|virus]].<ref name="pmid32277751" />
Total or parcial loss of olfactory function ([[anosmia]]/hyposmia) has been formally recognized as a characteristic [[symptom]] of [[COVID-19]] [[infection]], and may be the most common [[Sign (medicine)|sign]] of [[infection]] due to this [[Virus (biology)|virus]]. [[Anosmia]] may appear without any other [[Symptom|symptoms]] or [[Medical sign|signs]] in patients with [[COVID-19]] [[infection]]. The extent of potential [[olfactory]] [[dysfunction]] due to [[COVID-19]] is still unclear. [[Female]] [[Gender-based medicine|gender]] and [[Old age|advanced age]] are [[Risk factor|risk factors]] for developing [[anosmia]] related to [[COVID-19|COVID-19.]] [[Anosmia]] related to [[COVID-19]], typically has a duration of 8.96 days.


The extent of potential [[olfactory]] [[dysfunction]] due to [[COVID-19]] is still unclear.<ref name="pmid32563019" />
To view the complete page of COVID-19, [[COVID-19|click here]].


==Historical Perspective==
==Historical Perspective==


* [[COVID-19]] ([[SARS-CoV-2]]) [[outbreak]] initiated in December, 2019 in Wuhan, Hubei Province, China.<ref name="pmid32563019">{{cite journal |vauthors=Meng X, Deng Y, Dai Z, Meng Z |title=COVID-19 and anosmia: A review based on up-to-date knowledge |journal=Am J Otolaryngol |volume=41 |issue=5 |pages=102581 |date=June 2020 |pmid=32563019 |pmc=7265845 |doi=10.1016/j.amjoto.2020.102581 |url=}}</ref>  
*[[COVID-19]] ([[SARS-CoV-2]]) [[outbreak]] initiated and was discovered in December, 2019 in Wuhan, Hubei Province, China.<ref name="pmid32563019">{{cite journal |vauthors=Meng X, Deng Y, Dai Z, Meng Z |title=COVID-19 and anosmia: A review based on up-to-date knowledge |journal=Am J Otolaryngol |volume=41 |issue=5 |pages=102581 |date=June 2020 |pmid=32563019 |pmc=7265845 |doi=10.1016/j.amjoto.2020.102581 |url=}}</ref>
*On March 12, 2020, the World Health Organization declared the [[COVID-19]] outbreak a [[pandemic]].
*In April 17, 2020 Moein et al. demostrated a pronounced relation of [[olfactory]] [[dysfunction]] in patients with [[COVID-19]] [[infection]].<ref name="MoeinHashemian20202">{{cite journal|last1=Moein|first1=Shima T.|last2=Hashemian|first2=Seyed MohammadReza|last3=Mansourafshar|first3=Babak|last4=Khorram‐Tousi|first4=Ali|last5=Tabarsi|first5=Payam|last6=Doty|first6=Richard L.|title=Smell dysfunction: a biomarker for COVID‐19|journal=International Forum of Allergy & Rhinology|year=2020|issn=2042-6976|doi=10.1002/alr.22587}}</ref>
*In April 17, Shweta et al. used [[Artificial intelligence systems integration|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]].<ref name="url[2004.09338] Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis">{{cite web |url=https://arxiv.org/abs/2004.09338 |title=[2004.09338] Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis |format= |work= |accessdate=}}</ref><ref name="pmid32563019" />
*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%).<ref name="Beltrán‐CorbelliniChico‐García20202">{{cite journal|last1=Beltrán‐Corbellini|first1=Á.|last2=Chico‐García|first2=J. L.|last3=Martínez‐Poles|first3=J.|last4=Rodríguez‐Jorge|first4=F.|last5=Natera‐Villalba|first5=E.|last6=Gómez‐Corral|first6=J.|last7=Gómez‐López|first7=A.|last8=Monreal|first8=E.|last9=Parra‐Díaz|first9=P.|last10=Cortés‐Cuevas|first10=J. L.|last11=Galán|first11=J. C.|last12=Fragola‐Arnau|first12=C.|last13=Porta‐Etessam|first13=J.|last14=Masjuan|first14=J.|last15=Alonso‐Cánovas|first15=A.|title=Acute‐onset smell and taste disorders in the context of COVID‐19: a pilot multicentre polymerase chain reaction based case–control study|journal=European Journal of Neurology|year=2020|issn=1351-5101|doi=10.1111/ene.14273}}</ref>
*To view the historical perspective of COVID-19, [[COVID-19 historical perspective|click here]].


==Classification==
==Classification==


* There is no established system for the classification of [[COVID-19]] associated [[anosmia]].
* COVID-19 associated olfactory dysfunction may be classified as:
**[[Anosmia]]. Total incapacity for [[odor]] perception.<ref name="pmid32466862" />
**[[Hyposmia]].Increased [[odor]] detection [[Threshold Limit Value|threshold]].<ref name="pmid32466862" /> This is the most common type of olfactory dysfunction in patients with [[COVID-19]].
**[[Hyperosmia]].Decreased odor detection threshold.<ref name="pmid32466862" />
**[[Dysosmia]]. It is a [[qualitative]] alteration of [[smell]], where there is an incorrect identification of [[Odor|odors]].<ref name="pmid32466862" /> At the same time, [[Dysosmia|dysosmias]] can be classified as:
***[[Parosmia|Parosmias]]. Altered [[perception]] of an [[odor]] when stimulus is present .
***[[Phantosmia|Phantosmias]]. Perception of an [[odor]] without real [[stimulation]].
*To view the classification of COVID-19, [[COVID-19 classification|click here]].


==Pathophysiology==
==Pathophysiology==


*The pathogenesis of [[anosmia]] associated to [[COVID-19]] is characterized by total loss o<nowiki/>f olfaction due to afection to the [[olfactory bulb]].<ref name="pmid32563019" />
*The extent of potential [[olfactory]] [[dysfunction]] due to [[COVID-19]] is still unclear.<ref name="pmid32563019" /><ref name="pmid29528615">{{cite journal |vauthors=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 |title=Position paper on olfactory dysfunction |journal=Rhinol. Suppl. |volume=54 |issue=26 |pages=1–30 |date=March 2017 |pmid=29528615 |doi=10.4193/Rhino16.248 |url=}}</ref><nowiki/>
*The extent of potential [[olfactory]] [[dysfunction]] due to [[COVID-19]] is still unclear.<ref name="pmid32563019" /><ref name="pmid29528615">{{cite journal |vauthors=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 |title=Position paper on olfactory dysfunction |journal=Rhinol. Suppl. |volume=54 |issue=26 |pages=1–30 |date=March 2017 |pmid=29528615 |doi=10.4193/Rhino16.248 |url=}}</ref><nowiki/>
*Now in day, more than 200 types of [[viruses]] are identified to cause [[anosmia]]; [[coronavirus|coronav]]<nowiki/>[[coronavirus|irus]] [[Strain (biology)|strains]] (7 of them) are responsable of 10-15% of the cases.<ref name="pmid32277751">{{cite journal |vauthors=Hopkins C, Surda P, Kumar N |title=Presentation of new onset anosmia during the COVID-19 pandemic |journal=Rhinology |volume=58 |issue=3 |pages=295–298 |date=June 2020 |pmid=32277751 |doi=10.4193/Rhin20.116 |url=}}</ref><ref name="pmid16253889">{{cite journal |vauthors=Eccles R |title=Understanding the symptoms of the common cold and influenza |journal=Lancet Infect Dis |volume=5 |issue=11 |pages=718–25 |date=November 2005 |pmid=16253889 |pmc=7185637 |doi=10.1016/S1473-3099(05)70270-X |url=}}</ref><ref name="pmid32563019" /> <nowiki/>
*[[Pathogenicity]], [[virology]], and predi<nowiki/>lection for [[infection]] site are different for every [[virus]]. The main pathogenic site for [[COVID-19]] is [[throat]] and [[nose]].<ref name="pmid32303590">{{cite journal |vauthors=Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba NMA, 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 |title=Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model |journal=Science |volume=368 |issue=6494 |pages=1012–1015 |date=May 2020 |pmid=32303590 |pmc=7164679 |doi=10.1126/science.abb7314 |url=}}</ref><ref name="pmid32563019" />
*It is thought that the [[Genotype|genotypes]] o<nowiki/>f A and C [[Strain (biology)|strains]] of [[COVID-19|SARS-Cov]][[COVID-19|-2]] have a greater [[pathogenicity]] for the nasal cavity in humans, this explains the higher [[incidence]] of [[anosmia]] in European countries, where these [[Strain (biology)|strains]] prevail.<ref name="pmid32563019" /><ref name="ForsterForster2020">{{cite journal|last1=Forster|first1=Peter|last2=Forster|first2=Lucy|last3=Renfrew|first3=Colin|last4=Forster|first4=Michael|title=Phylogenetic network analysis of SARS-CoV-2 genomes|journal=Proceedings of the National Academy of Sciences|volume=117|issue=17|year=2020|pages=9241–9243|issn=0027-8424|doi=10.1073/pnas.2004999117}}</ref>
*The [[genome]] sequence of (COVID-19) <nowiki/>[[SARS-CoV-2]] is a 29,903 bp single-stranded [[RNA]].<ref name="pmid32563019" /><ref name="pmid32167747">{{cite journal |vauthors=Baig AM, Khaleeq A, Ali U, Syeda H |title=Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms |journal=ACS Chem Neurosci |volume=11 |issue=7 |pages=995–998 |date=April 2020 |pmid=32167747 |pmc=7094171 |doi=10.1021/acschemneuro.0c00122 |url=}}</ref>
*The [[genome]] sequence of (COVID-19) <nowiki/>[[SARS-CoV-2]] is a 29,903 bp single-stranded [[RNA]].<ref name="pmid32563019" /><ref name="pmid32167747">{{cite journal |vauthors=Baig AM, Khaleeq A, Ali U, Syeda H |title=Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms |journal=ACS Chem Neurosci |volume=11 |issue=7 |pages=995–998 |date=April 2020 |pmid=32167747 |pmc=7094171 |doi=10.1021/acschemneuro.0c00122 |url=}}</ref>
*[[Pathogenicity]], [[virology]], and predi<nowiki/>lection for [[infection]] site are different for every [[virus]]. The main pathogenic site for [[COVID-19]] is [[throat]] and [[nose]].<ref name="pmid32303590">{{cite journal |vauthors=Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba NMA, 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 |title=Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model |journal=Science |volume=368 |issue=6494 |pages=1012–1015 |date=May 2020 |pmid=32303590 |pmc=7164679 |doi=10.1126/science.abb7314 |url=}}</ref><ref name="pmid32563019" />
*[[Viral load|Viral loads]] of COVID-19 are higher<nowiki/> in the [[nasal cavity]] than any other site of [[infection]] ([[throat]], [[lungs]]), both, in [[symptomatic]] and [[asymptomatic]] individuals.<ref name="pmid32074444">{{cite journal |vauthors=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 |title=SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients |journal=N. Engl. J. Med. |volume=382 |issue=12 |pages=1177–1179 |date=March 2020 |pmid=32074444 |pmc=7121626 |doi=10.1056/NEJMc2001737 |url=}}</ref><ref name="pmid32563019" /><br />
*[[Viral load|Viral loads]] of COVID-19 are higher<nowiki/> in the [[nasal cavity]] than any other site of [[infection]] ([[throat]], [[lungs]]), both, in [[symptomatic]] and [[asymptomatic]] individuals.<ref name="pmid32074444">{{cite journal |vauthors=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 |title=SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients |journal=N. Engl. J. Med. |volume=382 |issue=12 |pages=1177–1179 |date=March 2020 |pmid=32074444 |pmc=7121626 |doi=10.1056/NEJMc2001737 |url=}}</ref><ref name="pmid32563019" />
 
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*Due to the special anatomy of the [[olfactory system]], [[COVID-19]] [[Virus (biology)|vi]][[Virus (biology)|rus]] may invade the [[Central nervous system infection|central nervous system infections]] via the [[cribriform plate]].<ref name="pmid32563019" /><ref name="pmid23601101">{{cite journal |vauthors=Koyuncu OO, Hogue IB, Enquist LW |title=Virus infections in the nervous system |journal=Cell Host Microbe |volume=13 |issue=4 |pages=379–93 |date=April 2013 |pmid=23601101 |pmc=3647473 |doi=10.1016/j.chom.2013.03.010 |url=}}</ref>
*Due to the special anatomy of the [[olfactory system]], [[COVID-19]] [[Virus (biology)|vi]][[Virus (biology)|rus]] may invade the [[Central nervous system infection|central nervous system infections]] via the [[cribriform plate]].<ref name="pmid32563019" /><ref name="pmid23601101">{{cite journal |vauthors=Koyuncu OO, Hogue IB, Enquist LW |title=Virus infections in the nervous system |journal=Cell Host Microbe |volume=13 |issue=4 |pages=379–93 |date=April 2013 |pmid=23601101 |pmc=3647473 |doi=10.1016/j.chom.2013.03.010 |url=}}</ref>
*It is thought that [[Goblet cell|Goblet cells]] and [[ciliated cells]] of the [[nasal mucosa]] may be the initial site of [[COVID-19]] infection when [[transmission]] is through airway.<ref name="pmid32563019" /><ref name="pmid32327758">{{cite journal |vauthors=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 |title=SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes |journal=Nat. Med. |volume=26 |issue=5 |pages=681–687 |date=May 2020 |pmid=32327758 |doi=10.1038/s41591-020-0868-6 |url=}}</ref>
*It is thought that [[Goblet cell|Goblet cells]] and [[ciliated cells]] of the [[nasal mucosa]] may be the initial site of [[COVID-19]] infection when [[transmission]] is through airway.<ref name="pmid32563019" /><ref name="pmid32327758">{{cite journal |vauthors=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 |title=SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes |journal=Nat. Med. |volume=26 |issue=5 |pages=681–687 |date=May 2020 |pmid=32327758 |doi=10.1038/s41591-020-0868-6 |url=}}</ref>
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>Studies suggest that [[viruses]] may propagate from the [[Nasal cavity|nasal cavit]]<nowiki/>y to the [[olfactory bulb]] through neuron-to-neuron [[axonal]] transport or passive diffusion of released viral particles.<ref name="pmid29925652" />
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>Studies suggest that [[viruses]] may propagate from the [[Nasal cavity|nasal cavit]]<nowiki/>y to the [[olfactory bulb]] through neuron-to-neuron [[axonal]] transport, passive diffusion of released viral particles, or hematogenously.<ref name="pmid29925652" /><ref name="CapelliGatti2020">{{cite journal|last1=Capelli|first1=Marco|last2=Gatti|first2=Patrizia|title=Anosmia and COVID-19 in south Lombardy: description of the first cases series in Europe|journal=B-ENT|volume=16|issue=1|year=2020|pages=86–90|issn=26844907|doi=10.5152/B-ENT.2020.20129}}</ref>
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>Several theories have been given to explain the variation of [[Incidence|in]]<nowiki/>[[Incidence|cidence]] of [[Olfaction|olfactory]] [[dysfunction]] among different countries, among these reasons are the [[pathogenicity]] and [[mutation]] capability of [[COVID-19]].<ref name="YaoLu2020">{{cite journal|last1=Yao|first1=Hangping|last2=Lu|first2=Xiangyun|last3=Chen|first3=Qiong|last4=Xu|first4=Kaijin|last5=Chen|first5=Yu|last6=Cheng|first6=Linfang|last7=Liu|first7=Fumin|last8=Wu|first8=Zhigang|last9=Wu|first9=Haibo|last10=Jin|first10=Changzhong|last11=Zheng|first11=Min|last12=Wu|first12=Nanping|last13=Jiang|first13=Chao|last14=Li|first14=Lanjuan|year=2020|doi=10.1101/2020.04.14.20060160}}</ref><ref name="pmid32563019" /><ref name="urlwww.thelancet.com">{{cite web |url=https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30079-5/Abstract |title=www.thelancet.com |format= |work= |accessdate=}}</ref><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>
*<nowiki/><nowiki/><nowiki/><nowiki/><nowiki/>To view the pathophysiology of COVID-19, [[COVID-19 pathophysiology|click here]].


==Causes==
==Causes==
Human [[Strain (biology)|strains]] of [[Coronavirus, SARS associated|coronavirus]] ([[Novel human coronavirus infection|HCoV]]<nowiki/>s) can infect and spread through the [[olfactory bulb]].<ref name="pmid29925652" /><ref name="pmid32277751" />


Now in day, more than 200 types of [[viruses]] are identified to cause [[anosmia]]; [[coronavirus]] [[Strain (biology)|strains]] (7 of them) are responsable of 10-15% of the cases.<ref name="pmid32277751" /><ref name="pmid16253889">{{cite journal |vauthors=Eccles R |title=Understanding the symptoms of the common cold and influenza |journal=Lancet Infect Dis |volume=5 |issue=11 |pages=718–25 |date=November 2005 |pmid=16253889 |pmc=7185637 |doi=10.1016/S1473-3099(05)70270-X |url=}}</ref><ref name="pmid32563019" />
*[[Anosmia]] associated to [[COVID-19]] is<nowiki/> caused by human [[Strain (biology)|strains]] of [[Coronavirus, SARS associated|coronavirus]] ([[Novel human coronavirus infection|HCoV]]<nowiki/>s) that infect and spread through the [[olfactory bulb]].<ref name="pmid29925652" /><ref name="pmid32277751" /><ref name="pmid172776212">{{cite journal |vauthors=Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, Murakami S |title=Identification of viruses in patients with postviral olfactory dysfunction |journal=Laryngoscope |volume=117 |issue=2 |pages=272–7 |date=February 2007 |pmid=17277621 |pmc=7165544 |doi=10.1097/01.mlg.0000249922.37381.1e |url=}}</ref>
 
*To view causes of COVID-19, [[COVID-19 causes|click here]].


==Differentiating COVID-19-associated anosmia from other Diseases==
==Differentiating COVID-19-associated anosmia from other Diseases==
<br />
 
*[[Anosmia]] associated to [[COVID-19]] must be differentiated from other diseases that cause acute [[smell]] loss.
*When differentiating [[anosmia]] due to [[COVID-19]] [[infection]] from other causes, it is important to pay attention into the presentation:
**Acute [[smell]] loss (other [[Upper respiratory infections|upper respiratory viral infections]], head injuries).<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
**Chronic [[smell]] loss (normal aging, [[rhinitis]], [[Nasal polyp|nasal polyps]], [[neoplasms]], [[Neurodegenerative disease|neurodegenerative disorders]]).<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
**Intermittent [[Smell Loss|smell loss]] ([[allergic rhinitis]], use of [[Topical application|topical]] drugs).<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
**Congenital [[smell]] loss ([[Kallmann syndrome]]).<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
*To view the differential diagnosis of COVID-19, [[COVID-19 differential diagnosis|click here]].<br />


==Epidemiology and Demographics==
==Epidemiology and Demographics==


* Postviral [[anosmia]] constitutes 40% of all [[anosmia]] causes in adults.<ref name="pmid32277751">{{cite journal |vauthors=Hopkins C, Surda P, Kumar N |title=Presentation of new onset anosmia during the COVID-19 pandemic |journal=Rhinology |volume=58 |issue=3 |pages=295–298 |date=June 2020 |pmid=32277751 |doi=10.4193/Rhin20.116 |url=}}</ref><ref>{{Cite journal|last=Zhu N, Zhang D, Wang W et al. A Novel Welge -Lussen A, Wolfensberger M.|first=|date=2006|title=Olfactory disorders following upper respiratory tract infections|url=|journal=Adv Otorhinolaryngol|volume=|pages=|via=}}</ref>
*The [[prevalence]] of [[anosmia]] related to [[COVID-19]] vary widely from one study to the other among several countries:<ref name="MenniValdes2020">{{cite journal|last1=Menni|first1=Cristina|last2=Valdes|first2=Ana|last3=Freydin|first3=Maxim B|last4=Ganesh|first4=Sajaysurya|last5=El-Sayed Moustafa|first5=Julia|last6=Visconti|first6=Alessia|last7=Hysi|first7=Pirro|last8=Bowyer|first8=Ruth C E|last9=Mangino|first9=Massimo|last10=Falchi|first10=Mario|last11=Wolf|first11=Jonathan|last12=Steves|first12=Claire|last13=Spector|first13=Tim|year=2020|doi=10.1101/2020.04.05.20048421}}</ref>
* Severe [[Olfaction|olfactory]] loss (complete [[anosmia]]) is estimated to have an estimated [[prevalence]] of around 5% in general population studies (independently of infection).<ref name="pmid32277751" /><ref name="pmid15064632">{{cite journal |vauthors=Brämerson A, Johansson L, Ek L, Nordin S, Bende M |title=Prevalence of olfactory dysfunction: the skövde population-based study |journal=Laryngoscope |volume=114 |issue=4 |pages=733–7 |date=April 2004 |pmid=15064632 |doi=10.1097/00005537-200404000-00026 |url=}}</ref>
*Further studies are requiered to establish the incidence of [[anosmia]] in [[COVID-19]]+ patients.<ref name="pmid32277751" />
*The [[incidence]] of [[anosmia]] related to [[COVID-19]] vary widely from one study to the other:


** A  study from Germany described that approximately two thirds of confirmed [[COVID-19]] infections presented [[anosmia]] and [[dysgeusia]] at some point of the [[disease]].<ref name="urlNeue Corona-Symptome entdeckt: Virologe Hendrik Streeck zum Virus">{{cite web |url=https://www.faz.net/aktuell/gesellschaft/gesundheit/coronavirus/neue-corona-symptome-entdeckt-virologe-hendrik-streeck-zum-virus-16681450.html |title=Neue Corona-Symptome entdeckt: Virologe Hendrik Streeck zum Virus |format= |work= |accessdate=}}</ref>  
{| class="wikitable"
** A study from South Korea, with 3191 mild-[[disease]] patients reported only 15.3% of [[anosmia]] or [[dysgeusia]].<ref name="url[단독]대구 확진자 3191명 중 15%, 후각이나 미각 잃었다 - 중앙일보">{{cite web |url=https://news.joins.com/article/23738003?cloc=joongang-mhomegroup6&fbclid=IwAR33__i-aKtLN2MzCs5A |title=[단독]대구 확진자 3191명 중 15%, 후각이나 미각 잃었다 - 중앙일보 |format= |work= |accessdate=}}</ref>
|+Prevalence of anosmia in patients with COVID-19<ref name="pmid32563019" />
** In a [[Retrospective study|retrospective]] study made by Klopfenstein et al., 54 (47%) out of 114 confirmed [[COVID-19]] patients presented with [[anosmia]].<ref name="pmid32305563">{{cite journal |vauthors=Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S |title=Features of anosmia in COVID-19 |journal=Med Mal Infect |volume= |issue= |pages= |date=April 2020 |pmid=32305563 |pmc=7162775 |doi=10.1016/j.medmal.2020.04.006 |url=}}</ref>
!Date of publication
* The [[prevalence]] of [[anosmia]] related to [[COVID-19]] has also varied from one country to another:
!Country
!Author
!Number of patients
!Prevalence
|-
|March 26, 2020
|Italy
|Giacomelli et al.<ref name="pmid32215618">{{cite journal |vauthors=Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M |title=Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study |journal=Clin. Infect. Dis. |volume= |issue= |pages= |date=March 2020 |pmid=32215618 |pmc=7184514 |doi=10.1093/cid/ciaa330 |url=}}</ref>
|59
|33.9%
|-
|March 27, 2020
|Iran
|Bagheri et al.<ref name="BagheriAsghari2020">{{cite journal|last1=Bagheri|first1=Seyed Hamid Reza|last2=Asghari|first2=Ali Mohammad|last3=Farhadi|first3=Mohammad|last4=Shamshiri|first4=Ahmad Reza|last5=Kabir|first5=Ali|last6=Kamrava|first6=Seyed Kamran|last7=Jalessi|first7=Maryam|last8=Mohebbi|first8=Alireza|last9=Alizadeh|first9=Rafieh|last10=Honarmand|first10=Ali Asghar|last11=Ghalehbaghi|first11=Babak|last12=Salimi|first12=Alireza|year=2020|doi=10.1101/2020.03.23.20041889}}</ref>
|10,069
|48.23%
|-
|April 1, 2020
|Italy
|Vaira et al.<ref name="pmid32237238">{{cite journal |vauthors=Vaira LA, Salzano G, Deiana G, De Riu G |title=Anosmia and Ageusia: Common Findings in COVID-19 Patients |journal=Laryngoscope |volume=130 |issue=7 |pages=1787 |date=July 2020 |pmid=32237238 |pmc=7228304 |doi=10.1002/lary.28692 |url=}}</ref>
|320
|19.4%
|-
|April 6, 2020
|European countries
|Lechien et al.<ref name="pmid32253535">{{cite journal |vauthors=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 |title=Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study |journal=Eur Arch Otorhinolaryngol |volume= |issue= |pages= |date=April 2020 |pmid=32253535 |pmc=7134551 |doi=10.1007/s00405-020-05965-1 |url=}}</ref>
|417
|85.6%
|-
|April 7, 2020
|United Kingdom
|Menni et al.<ref name="MenniValdes20202">{{cite journal|last1=Menni|first1=Cristina|last2=Valdes|first2=Ana|last3=Freydin|first3=Maxim B|last4=Ganesh|first4=Sajaysurya|last5=El-Sayed Moustafa|first5=Julia|last6=Visconti|first6=Alessia|last7=Hysi|first7=Pirro|last8=Bowyer|first8=Ruth C E|last9=Mangino|first9=Massimo|last10=Falchi|first10=Mario|last11=Wolf|first11=Jonathan|last12=Steves|first12=Claire|last13=Spector|first13=Tim|year=2020|doi=10.1101/2020.04.05.20048421}}</ref>
|579
|59.41%
|-
|April 12, 2020
|United States
|Yan et al.<ref name="pmid322794412">{{cite journal |vauthors=Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS |title=Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms |journal=Int Forum Allergy Rhinol |volume= |issue= |pages= |date=April 2020 |pmid=32279441 |pmc=7262089 |doi=10.1002/alr.22579 |url=}}</ref>
|59
|68%
|-
|April 16, 2020
|France
|Klopfenstein et al.<ref name="KlopfensteinKadiane-Oussou2020">{{cite journal|last1=Klopfenstein|first1=T.|last2=Kadiane-Oussou|first2=N.J.|last3=Toko|first3=L.|last4=Royer|first4=P.-Y.|last5=Lepiller|first5=Q.|last6=Gendrin|first6=V.|last7=Zayet|first7=S.|title=Features of anosmia in COVID-19|journal=Médecine et Maladies Infectieuses|year=2020|issn=0399077X|doi=10.1016/j.medmal.2020.04.006}}</ref>
|47
|47%
|-
|April 17, 2020
|Iran
|Moein et al.<ref name="MoeinHashemian20202" />
|60
|98.33%
|-
|April 22, 2020
|United Kingdom
|Spinato et al.<ref name="SpinatoFabbris2020">{{cite journal|last1=Spinato|first1=Giacomo|last2=Fabbris|first2=Cristoforo|last3=Polesel|first3=Jerry|last4=Cazzador|first4=Diego|last5=Borsetto|first5=Daniele|last6=Hopkins|first6=Claire|last7=Boscolo-Rizzo|first7=Paolo|title=Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection|journal=JAMA|volume=323|issue=20|year=2020|pages=2089|issn=0098-7484|doi=10.1001/jama.2020.6771}}</ref>
|202
|64.4%
|-
|April 22, 2020
|Iran
|Heidari et al.<ref name="HeidariKarimi2020">{{cite journal|last1=Heidari|first1=F.|last2=Karimi|first2=E.|last3=Firouzifar|first3=M.|last4=Khamushian|first4=P.|last5=Ansari|first5=R.|last6=Mohammadi Ardehali|first6=M.|last7=Heidari|first7=F.|title=Anosmia as a Prominent Symptom of COVID-19 Infection|journal=Rhinology journal|volume=58|issue=3|year=2020|pages=302–303|issn=03000729|doi=10.4193/Rhin20.140}}</ref>
|23
|69.57%
|-
|April 22, 2020
|Spain
|Beltran-Corbellini et al.<ref name="Beltrán‐CorbelliniChico‐García2020">{{cite journal|last1=Beltrán‐Corbellini|first1=Á.|last2=Chico‐García|first2=J. L.|last3=Martínez‐Poles|first3=J.|last4=Rodríguez‐Jorge|first4=F.|last5=Natera‐Villalba|first5=E.|last6=Gómez‐Corral|first6=J.|last7=Gómez‐López|first7=A.|last8=Monreal|first8=E.|last9=Parra‐Díaz|first9=P.|last10=Cortés‐Cuevas|first10=J. L.|last11=Galán|first11=J. C.|last12=Fragola‐Arnau|first12=C.|last13=Porta‐Etessam|first13=J.|last14=Masjuan|first14=J.|last15=Alonso‐Cánovas|first15=A.|title=Acute‐onset smell and taste disorders in the context of COVID‐19: a pilot multicentre polymerase chain reaction based case–control study|journal=European Journal of Neurology|year=2020|issn=1351-5101|doi=10.1111/ene.14273}}</ref>
|79
|31.65%
|-
|April 24, 2020
|United States
|Yan et al.<ref name="YanFaraji2020">{{cite journal|last1=Yan|first1=Carol H.|last2=Faraji|first2=Farhoud|last3=Prajapati|first3=Divya P.|last4=Ostrander|first4=Benjamin T.|last5=DeConde|first5=Adam S.|title=Self‐reported olfactory loss associates with outpatient clinical course in COVID‐19|journal=International Forum of Allergy & Rhinology|year=2020|issn=2042-6976|doi=10.1002/alr.22592}}</ref>
|169
|75.7%
|-
|May 1, 2020
|Germany
|Luers et al.<ref name="HeindlLehmann2020">{{cite journal|last1=Heindl|first1=Ludwig M|last2=Lehmann|first2=Clara|last3=Klein|first3=Florian|last4=Dewald|first4=Felix|last5=Augustin|first5=Max|last6=Wawer Matos|first6=Philomena A|last7=Loreck|first7=Niklas|last8=Rokohl|first8=Alexander C|last9=Luers|first9=Jan C|title=Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19)|journal=Clinical Infectious Diseases|year=2020|issn=1058-4838|doi=10.1093/cid/ciaa525}}</ref>
|72
|74%
|-
|May 1, 2020
|Italy
|Vaira et al.<ref name="VairaSalzano2020">{{cite journal|last1=Vaira|first1=Luigi Angelo|last2=Salzano|first2=Giovanni|last3=Petrocelli|first3=Marzia|last4=Deiana|first4=Giovanna|last5=Salzano|first5=Francesco Antonio|last6=De Riu|first6=Giacomo|title=Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine|journal=Head & Neck|year=2020|issn=10433074|doi=10.1002/hed.26228}}</ref>
|33
|75.8%
|}<br />


<br />
*Further studies are requiered to establish the [[incidence]] of [[anosmia]] in [[COVID-19]]+ patients.<ref name="pmid32277751" />
*Postviral [[anosmia]] constitutes 40% of all [[anosmia]] causes in adults.<ref name="pmid32277751" /><ref>{{Cite journal|last=Zhu N, Zhang D, Wang W et al. A Novel Welge -Lussen A, Wolfensberger M.|first=|date=2006|title=Olfactory disorders following upper respiratory tract infections|url=|journal=Adv Otorhinolaryngol|volume=|pages=|via=}}</ref>
* Severe [[Olfaction|olfactory]] loss (complete [[anosmia]]) is estimated to have an estimated [[prevalence]] of around 5% in general population studies (independently of [[infection]]).<ref name="pmid32277751" /><ref name="pmid15064632">{{cite journal |vauthors=Brämerson A, Johansson L, Ek L, Nordin S, Bende M |title=Prevalence of olfactory dysfunction: the skövde population-based study |journal=Laryngoscope |volume=114 |issue=4 |pages=733–7 |date=April 2004 |pmid=15064632 |doi=10.1097/00005537-200404000-00026 |url=}}</ref>
*To view screening for COVID-19, [[COVID-19 epidemiology and demographics|click here]].<br />


==Risk Factors==
==Risk Factors==
Line 60: Line 171:
* The most common identified [[risk factors]] for developing [[anosmia]] in patients with [[COVID-19]] infection are:<ref name="pmid32277751" /><ref name="pmid31693018">{{cite journal |vauthors=Stogbauer J, Wirkner K, Engel C, Moebus S, Pundt N, Teismann H, Loffler M, Hummel T, Beule AG, Berger K |title=Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies |journal=Rhinology |volume=58 |issue=2 |pages=184–191 |date=April 2020 |pmid=31693018 |doi=10.4193/Rhin19.181 |url=}}</ref><ref name="pmid31152646">{{cite journal |vauthors=Wang X, Zhang C, Xia X, Yang Y, Zhou C |title=Effect of gender on odor identification at different life stages: a meta-analysis |journal=Rhinology |volume=57 |issue=5 |pages=322–330 |date=October 2019 |pmid=31152646 |doi=10.4193/Rhin19.005 |url=}}</ref>
* The most common identified [[risk factors]] for developing [[anosmia]] in patients with [[COVID-19]] infection are:<ref name="pmid32277751" /><ref name="pmid31693018">{{cite journal |vauthors=Stogbauer J, Wirkner K, Engel C, Moebus S, Pundt N, Teismann H, Loffler M, Hummel T, Beule AG, Berger K |title=Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies |journal=Rhinology |volume=58 |issue=2 |pages=184–191 |date=April 2020 |pmid=31693018 |doi=10.4193/Rhin19.181 |url=}}</ref><ref name="pmid31152646">{{cite journal |vauthors=Wang X, Zhang C, Xia X, Yang Y, Zhou C |title=Effect of gender on odor identification at different life stages: a meta-analysis |journal=Rhinology |volume=57 |issue=5 |pages=322–330 |date=October 2019 |pmid=31152646 |doi=10.4193/Rhin19.005 |url=}}</ref>
** Advanced [[age]]<ref name="pmid31693018" />
** Advanced [[age]]<ref name="pmid31693018" />
** [[Male]] gender<ref name="pmid31152646" />
**[[Male|Female]] gender<ref name="pmid31152646" /><ref name="pmid32466862" />
**Genetic susceptibility
*Susceptibility to [[COVID-19]] [[infection]] is influenced to some degree by the [[Host (biology)|host]] [[genotype]], making a 47-fold [[heritability]] for [[anosmia]].<ref name="pmid32563019" /><ref name="WilliamsFreydin2020">{{cite journal|last1=Williams|first1=Frances MK|last2=Freydin|first2=Maxim|last3=Mangino|first3=Massimo|last4=Couvreur|first4=Simon|last5=Visconti|first5=Alessia|last6=Bowyer|first6=Ruth CE|last7=Le Roy|first7=Caroline I|last8=Falchi|first8=Mario|last9=Sudre|first9=Carole|last10=Davies|first10=Richard|last11=Hammond|first11=Christopher|last12=Menni|first12=Cristina|last13=Steves|first13=Claire|last14=Spector|first14=Tim|year=2020|doi=10.1101/2020.04.22.20072124}}</ref>
*To view the risk factors of COVID-19, [[COVID-19 risk factors|click here]].


==Screening==
==Screening==


* Several [[ENT]] societies in the United Kingdom and the United States, have advised to treat [[anosmia]] marker of [[SARS-CoV-2]] [[infection]].<ref name=":0">{{Cite journal|last=Robert Pellegrin, Keiland W. Cooper, Antonella Di Pizio, Paule V. Joseph, Surabhi Bhutani, Valentina Parma|first=|date=2020|title=Corona Viruses and the Chemical Senses:
*A [[Screening (medicine)|screening]] strategy, duly validated for [[Olfaction|olfactory]] [[disfunction]] in [[COVID-19]], consists of carrying out specific questionnaires, such as the ''Questionnaire for Olfactory Disfunction''.<ref name="pmid32466862" /><ref name="pmid26384780">{{cite journal |vauthors=Nguyen DT, Rumeau C, Gallet P, Jankowski R |title=Olfactory exploration: State of the art |journal=Eur Ann Otorhinolaryngol Head Neck Dis |volume=133 |issue=2 |pages=113–8 |date=April 2016 |pmid=26384780 |doi=10.1016/j.anorl.2015.08.038 |url=}}</ref><ref name="pmid22566102">{{cite journal |vauthors=Simopoulos E, Katotomichelakis M, Gouveris H, Tripsianis G, Livaditis M, Danielides V |title=Olfaction-associated quality of life in chronic rhinosinusitis: adaptation and validation of an olfaction-specific questionnaire |journal=Laryngoscope |volume=122 |issue=7 |pages=1450–4 |date=July 2012 |pmid=22566102 |doi=10.1002/lary.23349 |url=}}</ref>
*Several [[ENT]] societies in the United Kingdom and the United States, have advised treating [[anosmia]] marker of [[SARS-CoV-2]] [[infection]].<ref name=":0">{{Cite journal|last=Robert Pellegrin, Keiland W. Cooper, Antonella Di Pizio, Paule V. Joseph, Surabhi Bhutani, Valentina Parma|first=|date=2020|title=Corona Viruses and the Chemical Senses:
Past, Present, and Future|url=|journal=Oxford University|volume=|pages=|via=}}</ref><ref name="urlwww.entuk.org">{{cite web |url=https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf |title=www.entuk.org |format= |work= |accessdate=}}</ref><ref name="urlAAO-HNSF 2020 Annual Meeting & OTO Experience | American Academy of Otolaryngology-Head and Neck Surgery">{{cite web |url=https://www.entnet.org/content/aao-hnsf-2020-annual-meeting-oto-experience |title=AAO-HNSF 2020 Annual Meeting & OTO Experience &#124; American Academy of Otolaryngology-Head and Neck Surgery |format= |work= |accessdate=}}</ref>
Past, Present, and Future|url=|journal=Oxford University|volume=|pages=|via=}}</ref><ref name="urlwww.entuk.org">{{cite web |url=https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf |title=www.entuk.org |format= |work= |accessdate=}}</ref><ref name="urlAAO-HNSF 2020 Annual Meeting & OTO Experience | American Academy of Otolaryngology-Head and Neck Surgery">{{cite web |url=https://www.entnet.org/content/aao-hnsf-2020-annual-meeting-oto-experience |title=AAO-HNSF 2020 Annual Meeting & OTO Experience &#124; American Academy of Otolaryngology-Head and Neck Surgery |format= |work= |accessdate=}}</ref>
* 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.<ref name="urlAAO-HNSF 2020 Annual Meeting & OTO Experience | American Academy of Otolaryngology-Head and Neck Surgery" /><ref name=":0" />
* The [[American Academy of Otolaryngology]] (AAO) proposed for [[anosmia]], [[hyposmia]], and [[dysgeusia]] to be added to the list of [[Screening test|screening]] tools for [[COVID-19]] in otherwise [[asymptomatic]] individuals.<ref name="urlAAO-HNSF 2020 Annual Meeting & OTO Experience | American Academy of Otolaryngology-Head and Neck Surgery" /><ref name=":0" />
 
*In the absence of available solid data, the recommendation should be to perform nasal swabs on any patient with recent-onset [[anosmia]], duly assessed.<ref name="pmid32466862" />
<br />
*To view screening for COVID-19, [[COVID-19 screening|click here]].<br />


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
[[Anosmia]] related to [[COVID-19]], typically has a duration of 8.96 days.<ref name="pmid32563019" /><ref name="pmid323055632" />


Approximately 98% of patients with [[anosmia]] related to [[COVID-19]] recover within 28 days.<ref name="pmid32563019" /><ref name="pmid323055632" />
* Early clinical features before developing [[anosmia]] related to [[COVID-19]] include [[cough]], [[fever]], and [[Arthralgia|arthralgias]].
*[[Anosmia]] related to [[COVID-19]], typically has a duration of 8.96 days.<ref name="pmid32563019" /><ref name="pmid323055632" />
* Approximately 82% of patients with [[anosmia]] related to [[COVID-19]] recover within 2 weeks and 98% of them within 28 days.<ref name="pmid32563019" /><ref name="pmid323055632" /><ref name="pmid32279441">{{cite journal |vauthors=Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS |title=Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms |journal=Int Forum Allergy Rhinol |volume= |issue= |pages= |date=April 2020 |pmid=32279441 |pmc=7262089 |doi=10.1002/alr.22579 |url=}}</ref>
*The intensity and duration of the [[Olfaction|olfactory]] [[disfunction]] associated to [[COVID-19]], is highly variable depending on the capacity and rate of regeneration of the neuroepitielium.<ref name="pmid32466862" />
*A recent review by JAMA showed that 96% of the patients recover from [[anosmia]] within one year of its onset. At 6 months, 85% of the patients recovered from [[anosmia]]. [[Parosmia]] was not evaluated, and it can be potentially more debilitating for patients.<ref name="pmid34165581">{{cite journal| author=Renaud M, Thibault C, Le Normand F, Mcdonald EG, Gallix B, Debry C | display-authors=etal| title=Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis. | journal=JAMA Netw Open | year= 2021 | volume= 4 | issue= 6 | pages= e2115352 | pmid=34165581 | doi=10.1001/jamanetworkopen.2021.15352 | pmc=8226421 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34165581  }} </ref>
*To view natural history, complications, and prognosis of COVID-19, [[COVID-19 natural history, complications and prognosis|click here]].


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===
<br />
 
* [[Olfaction|Olfactory]] [[Function (biology)|function]] [[test]] (OFT) has been the study of choice for diagnosis of [[anosmia]] and [[olfactory]] [[dysfunction]].<ref name="OttavianoCarecchio2020">{{cite journal|last1=Ottaviano|first1=G.|last2=Carecchio|first2=M.|last3=Scarpa|first3=B.|last4=Marchese-Ragona|first4=R.|title=Olfactory and rhinological evaluations in SARS-CoV-2 patients complaining of olfactory loss|journal=Rhinology journal|volume=0|issue=0|year=2020|pages=0–0|issn=03000729|doi=10.4193/Rhin20.136}}</ref><ref name="pmid32563019" /><ref name="MoeinHashemian20202" /><ref name="VairaSalzano20202">{{cite journal|last1=Vaira|first1=Luigi Angelo|last2=Salzano|first2=Giovanni|last3=Petrocelli|first3=Marzia|last4=Deiana|first4=Giovanna|last5=Salzano|first5=Francesco Antonio|last6=De Riu|first6=Giacomo|title=Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine|journal=Head & Neck|year=2020|issn=10433074|doi=10.1002/hed.26228}}</ref>
* In many studies, full [[Olfaction|olfactory]] [[Function (biology)|function]] tests have been disregarded.<ref name="pmid32563019" />
*[[Olfaction|Olfactory]] [[Function (biology)|function]] [[test|tests]] is mainly carried out semi-quantitatively using olfactory bars or bottles kits, which are presented to the patient in order to determine the [[olfaction]] thresholds.<ref name="pmid32466862">{{cite journal |vauthors=Lop Gros J, Iglesias Coma M, González Farré M, Serra Pujadas C |title=Olfactory dysfunction in COVID-19, a review of the evidence and implications for pandemic management |journal=Acta Otorrinolaringol Esp |volume= |issue= |pages= |date=May 2020 |pmid=32466862 |doi=10.1016/j.otorri.2020.04.003 |url=}}</ref>
*Some of the most used [[Olfaction|olfactory]] [[Function (biology)|function]] [[test|tests]] are the University of Pennsylvania Smell Identification Test-40 and the Barcelona Smell Test-24, which respectively have 40 and 24 different [[Olfaction|olfactory]] [[stimuli]], and are therefore laborious and slow to administer.<ref name="pmid32466862" /><ref name="pmid17882917">{{cite journal |vauthors=Doty RL |title=Office procedures for quantitative assessment of olfactory function |journal=Am J Rhinol |volume=21 |issue=4 |pages=460–73 |date=2007 |pmid=17882917 |doi=10.2500/ajr.2007.21.3043 |url=}}</ref> For large series of patients evaluations the ''4-item Pocket Smell Test'' and the 12-item ''Brief Smell Identification Test'' are prefered.<ref name="pmid32466862" /><ref name="pmid31053960">{{cite journal |vauthors=Joseph T, Auger SD, Peress L, Rack D, Cuzick J, Giovannoni G, Lees A, Schrag AE, Noyce AJ |title=Screening performance of abbreviated versions of the UPSIT smell test |journal=J. Neurol. |volume=266 |issue=8 |pages=1897–1906 |date=August 2019 |pmid=31053960 |pmc=6647236 |doi=10.1007/s00415-019-09340-x |url=}}</ref>
*To view the study of choice for diagnosis of COVID-19, [[COVID-19 diagnostic study of choice|click here]].<br />


===History and Symptoms===
===History and Symptoms===


* [[Anosmia]] may occur suddenly as the only symptom of [[COVID-19]] in approximately 16% of individuals.<ref name="pmid32277751" /><ref name="pmid32319971">{{cite journal |vauthors=Heidari F, Karimi E, Firouzifar M, Khamushian P, Ansari R, Mohammadi Ardehali M, Heidari F |title=Anosmia as a prominent symptom of COVID-19 infection |journal=Rhinology |volume=58 |issue=3 |pages=302–303 |date=June 2020 |pmid=32319971 |doi=10.4193/Rhin20.140 |url=}}</ref>
* Approximately two thirds of confirmed [[COVID-19]] infections presented [[anosmia]] and [[dysgeusia]] at some point of the [[disease]].<ref name="urlNeue Corona-Symptome entdeckt: Virologe Hendrik Streeck zum Virus">{{cite web |url=https://www.faz.net/aktuell/gesellschaft/gesundheit/coronavirus/neue-corona-symptome-entdeckt-virologe-hendrik-streeck-zum-virus-16681450.html |title=Neue Corona-Symptome entdeckt: Virologe Hendrik Streeck zum Virus |format= |work= |accessdate=}}</ref>
 
*[[Anosmia]] may occur suddenly as the only symptom of [[COVID-19]] in approximately 16% of individuals.<ref name="pmid32277751" /><ref name="pmid32319971">{{cite journal |vauthors=Heidari F, Karimi E, Firouzifar M, Khamushian P, Ansari R, Mohammadi Ardehali M, Heidari F |title=Anosmia as a prominent symptom of COVID-19 infection |journal=Rhinology |volume=58 |issue=3 |pages=302–303 |date=June 2020 |pmid=32319971 |doi=10.4193/Rhin20.140 |url=}}</ref>
* In a study, 74.4% reported complete loss of [[smell]].<ref name="pmid32277751" />
* In a study, 74.4% reported complete loss of [[smell]].<ref name="pmid32277751" />
* [[Anosmia]] occurs more commonly after the onset of other [[symptoms]]. In a study involving 1325 participants with anosmia (with no confirmatory [[COVID-19 diagnostic study of choice|COVID-19 test]]), 13% reported [[anosmia]] before their onset, 38.4% at the same time, and in 48.6% after the onset of [[symptoms]].<ref name="pmid32277751" />
*[[Anosmia]] occurs more commonly after the onset of other [[symptoms]]. In a study involving 1325 participants with [[anosmia]] (with no confirmatory [[COVID-19 diagnostic study of choice|COVID-19 test]]), 13% reported [[anosmia]] before their onset, 38.4% at the same time, and in 48.6% after the onset of [[symptoms]].<ref name="pmid32277751" />
* A study reports that [[anosmia]] typically developes after 4.4 days of [[COVID-19]] [[infection]].<ref name="pmid323055632">{{cite journal |vauthors=Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S |title=Features of anosmia in COVID-19 |journal=Med Mal Infect |volume= |issue= |pages= |date=April 2020 |pmid=32305563 |pmc=7162775 |doi=10.1016/j.medmal.2020.04.006 |url=}}</ref><ref name="pmid32563019" />
* A study reports that [[anosmia]] typically developes after 4.4 days of [[COVID-19]] [[infection]].<ref name="pmid323055632">{{cite journal |vauthors=Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S |title=Features of anosmia in COVID-19 |journal=Med Mal Infect |volume= |issue= |pages= |date=April 2020 |pmid=32305563 |pmc=7162775 |doi=10.1016/j.medmal.2020.04.006 |url=}}</ref><ref name="pmid32563019" />
'''Common Symptoms'''
* Common symptoms accompanying [[anosmia]] related to [[COVID-19]] are:
** [[Fever]]
** [[Headache]]
** [[Nausea]]/ [[vomiting]]
** [[Irritability]]
** [[Malaise]]
** [[Neck stiffness]]
** Light sensitivity/ [[photophobia]]
'''Less Common Symptoms'''
* Less common symptoms accompanying [[anosmia]] related to [[COVID-19]] are:
** [[Myalgias]]
** [[Confusion]]
** [[Seizures]] (with concomitant [[encephalitis]])
*To view the history and symptoms of COVID-19, [[COVID-19 history and symptoms|click here]].


===Physical Examination===
===Physical Examination===
<br />
 
===== HEENT =====
 
*[[Physical examination]] using kits of different [[Olfaction|olfactory]] stimuli may disclose conductive, sensorineural, or mixed [[Olfaction|olfactory]] disfunction.<ref name="pmid32466862" />
* There is no typical physical finding for [[anosmia]] related to [[COVID-19]].
* To rule out other conditions physicians may:
 
** Closely inspect the nasal cavity and paranasal sinuses to look for polyps or neoplasms.<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
** Complete a neurological examination for neurodegenerative disorders.<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
** Do a fundoscopy for evidence of raised intracranial pressure due to head trauma.<ref name="urlAnosmia - StatPearls - NCBI Bookshelf" />
** Do skin prick testing for allergic rhinitis.<ref name="urlAnosmia - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK482152/ |title=Anosmia - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>
* To view the complete physical examination in COVID-19, [[COVID-19 physical examination|click here]].


===Laboratory Findings===
===Laboratory Findings===
<br />
 
* [[Laboratory diagnosis of virus|Laboratory testing]] and self-isolation should be made in patients who present with [[anosmia]], even if this is found as an isolated [[symptom]].<ref name="pmid32563019" />
* To view the laboratory findings on COVID-19, [[COVID-19 laboratory findings|click here]].


===Electrocardiogram===
===Electrocardiogram===
<br />
 
* There are no typical [[electrocardiographic]] findings for [[anosmia]] related to [[COVID-19]].
* To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]].<br />


===X-ray===
===X-ray===
<br />
 
*[[X-ray]] imaging to the [[nasal cavity]] and [[sinus]] (Cadwell and Waters projections) does not demonstrate any typical findings in patients with [[anosmia]] due to [[COVID-19]], but may be used to exclude other causes
* To view the x-ray finidings on COVID-19, [[COVID-19 x ray|click here]].<br />


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
<br />
 
* There are no typical [[Echocardiography|echocardiographic]] findings for [[anosmia]] related to [[COVID-19]].
* To view the echocardiographic findings on COVID-19, [[COVID-19 echocardiography and ultrasound|click here]].<br />


===CT scan===
===CT scan===
<br />
 
* [[Computed tomography|CT scan]] imaging to the [[nasal cavity]] and [[sinus]] may be used to exclude other causes, for example, a case report that revealed [[Inflammation|inflammatory]] blockage of the olfactory cleft in one patient.<ref name="pmid32563019" />
*To view the CT scan findings on COVID-19, [[COVID-19 CT scan|click here]].


===MRI===
===MRI===
<br />
 
*[[MRI]] imaging to the [[nasal cavity]] and [[sinus]] does not demonstrate any typical findings in patients with anosmia due to COVID-19 but may be used to exclude other causes.
* To view the MRI findings on COVID-19, [[COVID-19 MRI|click here]].<br />


===Other Imaging Findings===
===Other Imaging Findings===
<br />
 
*[[Ultrasound]] imaging to the [[nasal cavity]] and [[sinus]] does not demonstrate any typical findings in patients with anosmia due to [[COVID-19]] but may be used to exclude other causes.
* To view other imaging findings on COVID-19, [[COVID-19 other imaging findings|click here]].<br />


===Other Diagnostic Studies===
===Other Diagnostic Studies===
<br />
 
* To view other diagnostic studies for COVID-19, [[COVID-19 other diagnostic studies|click here]].<br />


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
<br />
 
* [[Oral steroids]] may be useful in patients with [[anosmia]] related to [[COVID-19]] after careful evaluation of [[risks]] and benefits, when duration exceeds 2 weeks. However, current [[World Health Organization|World Health Organization (WHO)]] guidelines advice to avoid the use of [[Oral steroids|systemic steroids]] when possible.<ref name="urlCoronavirus disease (COVID-19)">{{cite web |url=https://www.who.int/emergencies/diseases/novel-coronavirus-2019 |title=Coronavirus disease (COVID-19) |format= |work= |accessdate=}}</ref><ref name="pmid322777512">{{cite journal |vauthors=Hopkins C, Surda P, Kumar N |title=Presentation of new onset anosmia during the COVID-19 pandemic |journal=Rhinology |volume=58 |issue=3 |pages=295–298 |date=June 2020 |pmid=32277751 |doi=10.4193/Rhin20.116 |url=}}</ref> <ref name="pmid8560170">{{cite journal |vauthors=Ikeda K, Sakurada T, Suzaki Y, Takasaka T |title=Efficacy of systemic corticosteroid treatment for anosmia with nasal and paranasal sinus disease |journal=Rhinology |volume=33 |issue=3 |pages=162–5 |date=September 1995 |pmid=8560170 |doi= |url=}}</ref><ref name="pmid8560170" /><ref name="pmid319501562">{{cite journal |vauthors=Yan CH, Rathor A, Krook K, Ma Y, Rotella MR, Dodd RL, Hwang PH, Nayak JV, Oyesiku NM, DelGaudio JM, Levy JM, Wise J, Wise SK, Patel ZM |title=Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial |journal=Neurosurgery |volume= |issue= |pages= |date=January 2020 |pmid=31950156 |doi=10.1093/neuros/nyz559 |url=}}</ref><ref name="pmid31950156">{{cite journal |vauthors=Yan CH, Rathor A, Krook K, Ma Y, Rotella MR, Dodd RL, Hwang PH, Nayak JV, Oyesiku NM, DelGaudio JM, Levy JM, Wise J, Wise SK, Patel ZM |title=Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial |journal=Neurosurgery |volume= |issue= |pages= |date=January 2020 |pmid=31950156 |doi=10.1093/neuros/nyz559 |url=}}</ref><ref name="RedenLill2012">{{cite journal|last1=Reden|first1=Jens|last2=Lill|first2=Katja|last3=Zahnert|first3=Thomas|last4=Haehner|first4=Antje|last5=Hummel|first5=Thomas|title=Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: A double-blind, placebo-controlled, randomized clinical trial|journal=The Laryngoscope|volume=122|issue=9|year=2012|pages=1906–1909|issn=0023852X|doi=10.1002/lary.23405}}</ref><ref name="pmid12439184">{{cite journal |vauthors=Hummel T, Heilmann S, Hüttenbriuk KB |title=Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract |journal=Laryngoscope |volume=112 |issue=11 |pages=2076–80 |date=November 2002 |pmid=12439184 |doi=10.1097/00005537-200211000-00031 |url=}}</ref><ref name="pmid124391842">{{cite journal |vauthors=Hummel T, Heilmann S, Hüttenbriuk KB |title=Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract |journal=Laryngoscope |volume=112 |issue=11 |pages=2076–80 |date=November 2002 |pmid=12439184 |doi=10.1097/00005537-200211000-00031 |url=}}</ref><ref name="pmid28040824">{{cite journal |vauthors=Sorokowska A, Drechsler E, Karwowski M, Hummel T |title=Effects of olfactory training: a meta-analysis |journal=Rhinology |volume=55 |issue=1 |pages=17–26 |date=March 2017 |pmid=28040824 |doi=10.4193/Rhin16.195 |url=}}</ref><ref name="pmid32466862" /><ref name="pmid15563908">{{cite journal |vauthors=Seiden AM |title=Postviral olfactory loss |journal=Otolaryngol. Clin. North Am. |volume=37 |issue=6 |pages=1159–66 |date=December 2004 |pmid=15563908 |doi=10.1016/j.otc.2004.06.007 |url=}}</ref>
*[[Dosage]] has not been clarified by the source, but [[doses]] of 40–60 mg/day for 10–14 days of oral [[prednisolone]] have been shown to improve the mean [[Olfaction|olfactory]] recognition threshold in other causes of [[viral]] [[anosmia]].
* Olfactory training suggest small to moderate benefit for patients with post-viral [[Olfaction|olfactory]] [[dysfunction]].
*[[Alpha lipoic acid]] (600 mg/day), [[omega-3]] supplementation (2000mg/day),and intranasal [[Vitamin A derivatives|vitamin A]] (10,000 U/day)have been shown to improve objective tests of [[Olfaction|olfactory]] recovery in a small uncontrolled studies of patients with [[COVID-19]] related [[anosmia]], although, further investigation is needed before these therapies can be widely recomended.
*The main problem for the study of [[anosmia]] related to [[COVID-19]] treatment is that the majority of patients do not give importance to this [[symptom]] and recover [[spontaneously]], without [[medical attention]], so little evidence to support [[pharmacotherapy]] exists.
*To view medical treatment for COVID-19, click here.


===Surgery===
===Surgery===
<br />
 
* There are no [[surgical procedures]] for [[anosmia]] related to [[COVID-19]].<br />


===Primary Prevention===
===Primary Prevention===
<br />
 
*[[Telemedicine]] in [[otorhinolaryngology]] may be a good strategy for reducing [[cross-infection]] [[COVID-19]] in [[physicians]].<ref name="pmid32563019" /><ref name="MengDai2020">{{cite journal|last1=Meng|first1=Xiangming|last2=Dai|first2=Zhiyong|last3=Hang|first3=Chao|last4=Wang|first4=Yangyang|title=Smartphone-enabled wireless otoscope-assisted online telemedicine during the COVID-19 outbreak|journal=American Journal of Otolaryngology|volume=41|issue=3|year=2020|pages=102476|issn=01960709|doi=10.1016/j.amjoto.2020.102476}}</ref> <br />


===Secondary Prevention===
===Secondary Prevention===
* Self-administered [[Olfaction|olfactory]] [[Function (biology)|function]] tests can help the early detection of [[COVID-19]] and [[Isolation (health care)|isolation]].<ref name="pmid32563019" /><ref name="VairaSalzano20203">{{cite journal|last1=Vaira|first1=Luigi Angelo|last2=Salzano|first2=Giovanni|last3=Petrocelli|first3=Marzia|last4=Deiana|first4=Giovanna|last5=Salzano|first5=Francesco Antonio|last6=De Riu|first6=Giacomo|title=Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine|journal=Head & Neck|year=2020|issn=10433074|doi=10.1002/hed.26228}}</ref>
<br />
<br />


==References==
==References==
{{reflist|2}}
{{reflist|2}}
[[Category:Up-To-Date]]


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D. Fahimeh Shojaei, M.D.

Synonyms and keywords: anosmia, olfactory dysfunction, SARS-CoV-2, dysgeusia

Overview

Total or parcial loss of olfactory function (anosmia/hyposmia) 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. Anosmia may appear without any other symptoms or signs in patients with COVID-19 infection. The extent of potential olfactory dysfunction due to COVID-19 is still unclear. Female gender and advanced age are risk factors for developing anosmia related to COVID-19. Anosmia related to COVID-19, typically has a duration of 8.96 days.

To view the complete page of COVID-19, click here.

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating COVID-19-associated anosmia from other Diseases

Epidemiology and Demographics

Prevalence of anosmia in patients with COVID-19[1]
Date of publication Country Author Number of patients Prevalence
March 26, 2020 Italy Giacomelli et al.[22] 59 33.9%
March 27, 2020 Iran Bagheri et al.[23] 10,069 48.23%
April 1, 2020 Italy Vaira et al.[24] 320 19.4%
April 6, 2020 European countries Lechien et al.[25] 417 85.6%
April 7, 2020 United Kingdom Menni et al.[26] 579 59.41%
April 12, 2020 United States Yan et al.[27] 59 68%
April 16, 2020 France Klopfenstein et al.[28] 47 47%
April 17, 2020 Iran Moein et al.[2] 60 98.33%
April 22, 2020 United Kingdom Spinato et al.[29] 202 64.4%
April 22, 2020 Iran Heidari et al.[30] 23 69.57%
April 22, 2020 Spain Beltran-Corbellini et al.[31] 79 31.65%
April 24, 2020 United States Yan et al.[32] 169 75.7%
May 1, 2020 Germany Luers et al.[33] 72 74%
May 1, 2020 Italy Vaira et al.[34] 33 75.8%


Risk Factors

Screening

Natural History, Complications, and Prognosis

  • Early clinical features before developing anosmia related to COVID-19 include cough, fever, and arthralgias.
  • Anosmia related to COVID-19, typically has a duration of 8.96 days.[1][45]
  • Approximately 82% of patients with anosmia related to COVID-19 recover within 2 weeks and 98% of them within 28 days.[1][45][46]
  • The intensity and duration of the olfactory disfunction associated to COVID-19, is highly variable depending on the capacity and rate of regeneration of the neuroepitielium.[5]
  • A recent review by JAMA showed that 96% of the patients recover from anosmia within one year of its onset. At 6 months, 85% of the patients recovered from anosmia. Parosmia was not evaluated, and it can be potentially more debilitating for patients.[47]
  • To view natural history, complications, and prognosis of COVID-19, click here.

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Common Symptoms

Less Common Symptoms

  • To view the history and symptoms of COVID-19, click here.

Physical Examination

HEENT
    • Closely inspect the nasal cavity and paranasal sinuses to look for polyps or neoplasms.[20]
    • Complete a neurological examination for neurodegenerative disorders.[20]
    • Do a fundoscopy for evidence of raised intracranial pressure due to head trauma.[20]
    • Do skin prick testing for allergic rhinitis.[20]
  • To view the complete physical examination in COVID-19, click here.

Laboratory Findings

Electrocardiogram

X-ray

  • X-ray imaging to the nasal cavity and sinus (Cadwell and Waters projections) does not demonstrate any typical findings in patients with anosmia due to COVID-19, but may be used to exclude other causes
  • To view the x-ray finidings on COVID-19, click here.

Echocardiography or Ultrasound

CT scan

MRI

  • MRI imaging to the nasal cavity and sinus does not demonstrate any typical findings in patients with anosmia due to COVID-19 but may be used to exclude other causes.
  • To view the MRI findings on COVID-19, click here.

Other Imaging Findings

  • Ultrasound imaging to the nasal cavity and sinus does not demonstrate any typical findings in patients with anosmia due to COVID-19 but may be used to exclude other causes.
  • To view other imaging findings on COVID-19, click here.

Other Diagnostic Studies

  • To view other diagnostic studies for COVID-19, click here.

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention


References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 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).
  2. 2.0 2.1 2.2 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.
  3. "[2004.09338] Augmented Curation of Unstructured Clinical Notes from a Massive EHR System Reveals Specific Phenotypic Signature of Impending COVID-19 Diagnosis".
  4. 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.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 Lop Gros J, Iglesias Coma M, González Farré M, Serra Pujadas C (May 2020). "Olfactory dysfunction in COVID-19, a review of the evidence and implications for pandemic management". Acta Otorrinolaringol Esp. doi:10.1016/j.otorri.2020.04.003. PMID 32466862 Check |pmid= value (help).
  6. 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.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 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).
  8. 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.
  9. 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)
  10. Forster, Peter; Forster, Lucy; Renfrew, Colin; Forster, Michael (2020). "Phylogenetic network analysis of SARS-CoV-2 genomes". Proceedings of the National Academy of Sciences. 117 (17): 9241–9243. doi:10.1073/pnas.2004999117. ISSN 0027-8424.
  11. 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).
  12. 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).
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