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===Medical Therapy=== | ===Medical Therapy=== | ||
* [[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. | * [[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="pmid8560170" /><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="pmid322777512" /><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="pmid8560170" /><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]]. | |||
*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. | *[[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. | *To view medical treatment for COVID-19, click here. | ||
Revision as of 13:27, 21 July 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo 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
- COVID-19 (SARS-CoV-2) outbreak initiated and was discovered in December, 2019 in Wuhan, Hubei Province, China.[1]
- 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.[2]
- 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.[3][1]
- 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%).[4]
- To view the historical perspective of COVID-19, click here.
Classification
- COVID-19 associated olfactory dysfunction may be classified as:
- Anosmia. Total incapacity for odor perception.[5]
- Hyposmia.Increased odor detection threshold.[5] This is the most common type of olfactory dysfunction in patients with COVID-19.
- Hyperosmia.Decreased odor detection threshold.[5]
- Dysosmia. It is a qualitative alteration of smell, where there is an incorrect identification of odors.[5] At the same time, dysosmias can be classified as:
- Parosmias. Altered perception of an odor when stimulus is present .
- Phantosmias. Perception of an odor without real stimulation.
- To view the classification of COVID-19, click here.
Pathophysiology
- The pathogenesis of anosmia associated to COVID-19 is characterized by total loss of olfaction due to afection to the olfactory bulb.[1]
- The extent of potential olfactory dysfunction due to COVID-19 is still unclear.[1][6]
- 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.[7][8][1]
- Pathogenicity, virology, and predilection for infection site are different for every virus. The main pathogenic site for COVID-19 is throat and nose.[9][1]
- It is thought that the genotypes of A and C strains of SARS-Cov-2 have a greater pathogenicity for the nasal cavity in humans, this explains the higher incidence of anosmia in European countries, where these strains prevail.[1][10]
- The genome sequence of (COVID-19) SARS-CoV-2 is a 29,903 bp single-stranded RNA.[1][11]
- 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.[12][1]
- The mechanism of central nervous system (CNS) invasion is unclear.[13]
- Due to the special anatomy of the olfactory system, COVID-19 virus may invade the central nervous system infections via the cribriform plate.[1][14]
- 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.[1][15]
- Studies suggest that viruses may propagate from the nasal cavity to the olfactory bulb through neuron-to-neuron axonal transport, passive diffusion of released viral particles, or hematogenously.[13][16]
- Several theories have been given to explain the variation of incidence of olfactory dysfunction among different countries, among these reasons are the pathogenicity and mutation capability of COVID-19.[17][1][18]
- To view the pathophysiology of COVID-19, click here.
Causes
- Anosmia associated to COVID-19 is caused by human strains of coronavirus (HCoVs) that infect and spread through the olfactory bulb.[13][7][19]
- To view causes of COVID-19, click here.
Differentiating COVID-19-associated anosmia from other Diseases
- 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 viral infections, head injuries).[20]
- Chronic smell loss (normal aging, rhinitis, nasal polyps, neoplasms, neurodegenerative disorders).[20]
- Intermittent smell loss (allergic rhinitis, use of topical drugs).[20]
- Congenital smell loss (Kallmann syndrome).[20]
- To view the differential diagnosis of COVID-19, click here.
Epidemiology and Demographics
- The prevalence of anosmia related to COVID-19 vary widely from one study to the other among several countries:[21]
| 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% |
- Further studies are requiered to establish the incidence of anosmia in COVID-19+ patients.[7]
- Postviral anosmia constitutes 40% of all anosmia causes in adults.[7][35]
- Severe olfactory loss (complete anosmia) is estimated to have an estimated prevalence of around 5% in general population studies (independently of infection).[7][36]
- To view screening for COVID-19, click here.
Risk Factors
- The most common identified risk factors for developing anosmia in patients with COVID-19 infection are:[7][37][38]
- Susceptibility to COVID-19 infection is influenced to some degree by the host genotype, making a 47-fold heritability for anosmia.[1][39]
- To view the risk factors of COVID-19, click here.
Screening
- A screening strategy, duly validated for olfactory disfunction in COVID-19, consists of carrying out specific questionnaires, such as the Questionnaire for Olfactory Disfunction.[5][40][41]
- Several ENT societies in the United Kingdom and the United States, have advised to treat anosmia marker of SARS-CoV-2 infection.[42][43][44]
- 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.[44][42]
- In the absence of available solid data, the recommendation should be to perform nasal swabs on any patient with recent onset anosmia, duly assessed.[5]
- To view screening for COVID-19, click here.
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]
- To view natural history, complications, and prognosis of COVID-19, click here.
Diagnosis
Diagnostic Study of Choice
- Olfactory function test (OFT) has been the study of choice for diagnosis of anosmia and olfactory dysfunction.[47][1][2][48]
- In many studies, full olfactory function tests have been disregarded.[1]
- Olfactory function 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.[5]
- Some of the most used olfactory function tests are the University of Pennsylvania Smell Identification Test-40 and the Barcelona Smell Test-24, which respectively have 40 and 24 different olfactory stimuli, and are therefore laborious and slow to administer.[5][49] For large series of patients evaluations the 4-item Pocket Smell Test and the 12-item Brief Smell Identification Test are prefered.[5][50]
- To view the study of choice for diagnosis of COVID-19, click here.
History and Symptoms
- Approximately two thirds of confirmed COVID-19 infections presented anosmia and dysgeusia at some point of the disease.[51]
- Anosmia may occur suddenly as the only symptom of COVID-19 in approximately 16% of individuals.[7][52]
- In a study, 74.4% reported complete loss of smell.[7]
- 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.[7]
- A study reports that anosmia typically developes after 4.4 days of COVID-19 infection.[45][1]
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, click here.
Physical Examination
- Physical examination using kits of different olfactory stimuli may disclose conductive, sensorineural, or mixed olfactory disfunction.[5]
- There is no typical physical finding for anosmia related to COVID-19.
- To rule out other conditions physicians may:
- To view the complete physical examination in COVID-19, click here.
Laboratory Findings
- Laboratory testing and self-isolation should be made in patients who present with anosmia, even if this is found as an isolated symptom.[1]
- To view the laboratory findings on COVID-19, click here.
Electrocardiogram
- There are no typical electrocardiographic findings for anosmia related to COVID-19.
- To view the electrocardiogram findings on COVID-19, click here.
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
- There are no typical echocardiographic findings for anosmia related to COVID-19.
- To view the echocardiographic findings on COVID-19, click here.
CT scan
- CT scan imaging to the nasal cavity and sinus may be used to exclude other causes, for example, a case report that revealed inflammatory blockage of the olfactory cleft in one patient.[1]
- To view the CT scan findings on COVID-19, click here.
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
- 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 (WHO) guidelines advice to avoid the use of systemic steroids when possible.[53][54] [55][55][56][57][55][58][54][59][55][60][61][5][62]
- 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 olfactory recognition threshold in other causes of viral anosmia.
- Olfactory training suggest small to moderate benefit for patients with post-viral olfactory dysfunction.
- Alpha lipoic acid (600 mg/day), omega-3 supplementation (2000mg/day),and intranasal vitamin A (10,000 U/day)have been shown to improve objective tests of 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
- There are no surgical procedures for anosmia related to COVID-19.
Primary Prevention
- Telemedicine in otorhinolaryngology may be a good strategy for reducing cross-infection COVID-19 in physicians.[1][63]
Secondary Prevention
- Self-administered olfactory function tests can help the early detection of COVID-19 and isolation.[1][64]
References
- ↑ 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). - ↑ 2.0 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.
- ↑ "[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.
- ↑ 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). - ↑ 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.
- ↑ 7.0 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). - ↑ 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. - ↑ 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) - ↑ 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.
- ↑ 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). - ↑ 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). - ↑ 13.0 13.1 13.2 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). - ↑ Capelli, Marco; Gatti, Patrizia (2020). "Anosmia and COVID-19 in south Lombardy: description of the first cases series in Europe". B-ENT. 16 (1): 86–90. doi:10.5152/B-ENT.2020.20129. ISSN 2684-4907.
- ↑ Yao, Hangping; Lu, Xiangyun; Chen, Qiong; Xu, Kaijin; Chen, Yu; Cheng, Linfang; Liu, Fumin; Wu, Zhigang; Wu, Haibo; Jin, Changzhong; Zheng, Min; Wu, Nanping; Jiang, Chao; Li, Lanjuan (2020). doi:10.1101/2020.04.14.20060160. Missing or empty
|title=(help) - ↑ "www.thelancet.com".
- ↑ Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, Murakami S (February 2007). "Identification of viruses in patients with postviral olfactory dysfunction". Laryngoscope. 117 (2): 272–7. doi:10.1097/01.mlg.0000249922.37381.1e. PMC 7165544 Check
|pmc=value (help). PMID 17277621. - ↑ 20.0 20.1 20.2 20.3 20.4 20.5 20.6 20.7 "Anosmia - StatPearls - NCBI Bookshelf".
- ↑ 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.
- ↑ 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.
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- ↑ 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) - ↑ Nguyen DT, Rumeau C, Gallet P, Jankowski R (April 2016). "Olfactory exploration: State of the art". Eur Ann Otorhinolaryngol Head Neck Dis. 133 (2): 113–8. doi:10.1016/j.anorl.2015.08.038. PMID 26384780.
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Past, Present, and Future". Oxford University. line feed character in
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|pmc=value (help). PMID 32305563 Check|pmid=value (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). - ↑ 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.
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|pmc=value (help). PMID 31053960. - ↑ "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). - ↑ 54.0 54.1 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). - ↑ 55.0 55.1 55.2 55.3 Ikeda K, Sakurada T, Suzaki Y, Takasaka T (September 1995). "Efficacy of systemic corticosteroid treatment for anosmia with nasal and paranasal sinus disease". Rhinology. 33 (3): 162–5. PMID 8560170.
- ↑ 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 (January 2020). "Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial". Neurosurgery. doi:10.1093/neuros/nyz559. PMID 31950156.
- ↑ 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 (January 2020). "Effect of Omega-3 Supplementation in Patients With Smell Dysfunction Following Endoscopic Sellar and Parasellar Tumor Resection: A Multicenter Prospective Randomized Controlled Trial". Neurosurgery. doi:10.1093/neuros/nyz559. PMID 31950156.
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- ↑ Hummel T, Heilmann S, Hüttenbriuk KB (November 2002). "Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract". Laryngoscope. 112 (11): 2076–80. doi:10.1097/00005537-200211000-00031. PMID 12439184.
- ↑ Hummel T, Heilmann S, Hüttenbriuk KB (November 2002). "Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract". Laryngoscope. 112 (11): 2076–80. doi:10.1097/00005537-200211000-00031. PMID 12439184.
- ↑ Sorokowska A, Drechsler E, Karwowski M, Hummel T (March 2017). "Effects of olfactory training: a meta-analysis". Rhinology. 55 (1): 17–26. doi:10.4193/Rhin16.195. PMID 28040824.
- ↑ Seiden AM (December 2004). "Postviral olfactory loss". Otolaryngol. Clin. North Am. 37 (6): 1159–66. doi:10.1016/j.otc.2004.06.007. PMID 15563908.
- ↑ Meng, Xiangming; Dai, Zhiyong; Hang, Chao; Wang, Yangyang (2020). "Smartphone-enabled wireless otoscope-assisted online telemedicine during the COVID-19 outbreak". American Journal of Otolaryngology. 41 (3): 102476. doi:10.1016/j.amjoto.2020.102476. ISSN 0196-0709.
- ↑ 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.