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Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 297-302

Management of olfactory dysfunction in COVID-19 patients: a review

Department of Otorhinolaryngology—Head and Neck Surgery, Institute of Medical Sciences and SUM Hospital, Siksha “O” Anusandhan (Deemed to be University), K8 Lane 1, Kalinganagar, Bhubaneswar 751003, Odisha, India

Date of Submission18-Jun-2021
Date of Acceptance27-Jul-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Prof. Santosh Kumar Swain
Department of Otorhinolaryngology—Head and Neck Surgery, Institute of Medical Sciences and SUM Hospital, Siksha “O” Anusandhan (Deemed to be University), K8 Lane 1, Kalinganagar, Bhubaneswar 751003, Odisha.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mgmj.mgmj_37_21

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Coronavirus disease 2019 (COVID-19) is a highly contagious infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptomatology of COVID-19 varies from mild symptoms such as fever and dry cough to severe acute respiratory distress syndrome (ARDS). There is an increasing number of patients with anosmia and hyposmia as the COVID-19 pandemic continues. Currently, loss of smell is a well-recognized symptom of the COVID-19 infection, and some of the patients develop long-lasting olfactory dysfunction. Some COVID-19 patients may present with olfactory dysfunction as the only symptom or with other symptoms. The exact pathogenesis of olfactory dysfunctions is still not clear. The clinical evolution of the olfactory dysfunction in COVID-19 patients is still unclear as the recovery reports vary significantly. There is no recommended standard treatment protocol to reduce anosmia or hyposmia due to COVID-19 infection. A short course of oral corticosteroids and olfactory training (OT) is a safe and effective option for managing post-COVID olfactory dysfunction. The efficacy of intranasal corticosteroid spray is still in doubt for treating olfactory dysfunction in COVID-19 patients. Currently, OT is a useful treatment option for anosmia or hyposmia in COVID-19 patients. However, there is a crucial need for further studies to get better and more effective treatment options for a complete cure of the post-COVID-19 olfactory dysfunction. This review article discusses the details of the management of olfactory dysfunction in COVID-19 patients. The literature sources included PubMed, Scopus, Google Scholar, and Medline databases and searched with word management of olfactory dysfunction in COVID-19 patients, smell disturbances, COVID-19 infections, olfactory dysfunction, and medical treatment of olfactory dysfunction.

Keywords: Corticosteroid, COVID-19, olfactory dysfunction, olfactory training, SARS-CoV-2

How to cite this article:
Swain SK. Management of olfactory dysfunction in COVID-19 patients: a review. MGM J Med Sci 2021;8:297-302

How to cite this URL:
Swain SK. Management of olfactory dysfunction in COVID-19 patients: a review. MGM J Med Sci [serial online] 2021 [cited 2022 Jan 25];8:297-302. Available from: http://www.mgmjms.com/text.asp?2021/8/3/297/325543

  Introduction Top

COVID-19 infection is a contagious disease and is considered a global public health emergency. The first case of COVID-19 infection was reported in Wuhan, Hubei Province of China in December 2019.[1] The etiological agent for this outbreak was a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[2] This SARS-CoV-2 virus is highly infectious and spreads all over the world. SARS-CoV-2 is the seventh member of the Coronaviridae family, a positive-sense RNA virus. COVID-19 patients often present with symptoms of respiratory tract infections such as fever, myalgia, dry cough, chest tightness, sore throat, nasal congestions, rhinorrhea, olfactory dysfunction, and dyspnea.[3] Olfaction is a part of the chemosensory system, which plays an important role in digestive behavior as it detects and enjoys food.[4] Olfaction is also important for social communication and the detection of environmental hazards.[4] COVID-19 pandemic is still ongoing, and several patients are complaining of sudden onset olfactory dysfunction. Although many patients recover from anosmia or hyposmia, a few of them are presenting persisting anosmia or parosmia and even phantosmia.[5] Currently, olfactory dysfunction is a well-recognized symptom of the COVID-19 patient. As the COVID-19 pandemic continues and the number of patients is increasing with complaints of olfactory loss, yet, there is no recommended standard treatment for olfactory dysfunction in COVID-19 patients. There are still debates going on for exact treatment of olfactory dysfunction in COVID-19 patients. There is not much literature for smell disturbances with robust epidemiological studies and management in COVID-19 patients, indicating that these medical entities are neglected in a current pandemic.

  Methods for literature search Top

The research articles related to the management of olfactory dysfunction in COVID-19 patients were searched through multiple approaches. First, we conducted an online search of the PubMed, Scopus, Google Scholar, and Medline databases with word management of olfactory dysfunction in COVID-19 patients, smell disturbances, COVID-19 infections, olfactory dysfunction, and medical treatment of olfactory dysfunction. A search strategy using Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines was developed. Randomized controlled studies, observational studies, comparative studies, case series, and case reports were evaluated for eligibility. This paper focusses only on the management of smell disorders/olfactory dysfunction in COVID-19 patients. Review articles with no primary research data were also excluded. The abstracts of the published articles were identified by this search method, and other articles were identified manually from the citations. This review article reviews the epidemiology, etiopathology, clinical manifestations, investigation, and treatment of smell disturbances or olfactory dysfunction by SARS-CoV-2 infections. This review article presents a baseline from where further prospective trials can be designed and help as a spur for further research in this important clinical aspect such as management of olfactory dysfunction of the COVID-19 patients where not many studies are done.

  Epidemiology Top

The World Health Organization officially declared the COVID-19 outbreak as a pandemic on March 11, 2020, where more than 200 countries were affected in the world.[6] By May 2020, more than 3,000,000 people have been infected with SARS-CoV-2.[7] The Centers for Disease Control and Prevention (CDC) has declared key symptoms of the COVID-19 infections which include fever, dry cough, dyspnea, myalgia, throat pain, and loss of smell and taste.[8] Olfactory and gustatory dysfunction are often considered biomarkers of COVID-19 infection. The British Rhinological Society (BRS) and ENTUK first time reported about the loss of smell and loss of taste as important symptoms in COVID-19 patients. There has been more evidence-based support of these initial observations made by BRS and ENTUK on olfactory and gustatory dysfunction in the COVID-19 pandemic.[8] Smell disorders or olfactory dysfunction is the most prevalent symptom of COVID-19 patients.[9] The self-reported loss of smell is found in approximately 50% of the COVID-19 patients.[10] Current data suggest a high early recovery rate; however, at 4–6 weeks after onset of the symptom, approximately 10% of the patients have not shown any recovery and still present with smell disturbances.[10] Olfactory dysfunction is defined as the distorted or reduced ability for smelling at the time of sniffing (ortho-nasal olfaction) or eating (retro-nasal olfaction) in mild or even asymptomatic cases. One study from Italy showed that 64% of mildly symptomatic patients presented with olfactory dysfunction.[11] Another study demonstrated that olfactory dysfunction was found in 85.6% and taste disturbances in 88.8% of the patients with COVID-19 infections.[12] Parma et al.[13] showed smell disturbances in 90.18% and taste disturbances in 91.44%. As there is a lack of studies with long-term follow-up for post-COVID olfactory dysfunction, the exact proportion of patients with post-infectious olfactory impairment is difficult to define in the current scenario.

  Etiopathology Top

Post-viral upper respiratory tract infection causing anosmia is an important cause for olfactory dysfunction in adults, which constitutes approximately 40% of the cases of anosmia.[14] Common cold or upper respiratory viral infections are considered a well-known etiology for post-infectious olfactory dysfunction, and it has an impact on quality of life.[14] Other than the anti-inflammatory mechanism of corticosteroids, local action of it is thought to enhance olfactory function by modulating the function of olfactory receptor neurons through olfactory Na-K-ATPase.[15] Another study showed the effects of topical and systemic corticosteroids in patients of olfactory dysfunction, in which they found the improvement of smell sensation after topical administration of mometasone nasal spray.[16] The improvement of the sense of smell depends on the cause of olfactory dysfunction such as idiopathic, upper respiratory tract infection, post-traumatic, and sinonasal diseases. A study showed that diabetes mellitus, age, and duration of COVID-19 infection can affect the duration of olfactory dysfunction, in which patients revealed that average time for recovery of olfactory dysfunction was 35.0±2.31 days in diabetic patients (P = 0.004) in comparison to 25.64±6.53 days in non-diabetic patients (P = 0.006).[17] Another study suggested that the absence of fever was the important prognostic factor for persistent olfactory dysfunction in COVID-19 patients.[18] Olfactory dysfunction is classified into two types such as conductive type (physical blockage of the nasal airflow to olfactory epithelium) and sensorineural type (disruption of the olfactory neural signaling pathway).[19] The virus might damage the olfactory epithelium and alter the number and functions of the olfactory receptors.[20] It is a hypothesis that the olfactory dysfunctions are not associated with definitive viral damage to the neuronal cells. Non-neuronal cells express angiotensin-converting enzyme 2 (ACE2) receptors which include olfactory epithelium sustentacular cells, microvillar cells, Bowman’s gland cells, horizontal basal cells, and olfactory bulb pericytes, and these are the targets of SARS-CoV-2.[21] In the case of long-standing anosmia and olfactory dysfunction, the involvement of stem cells which show lower levels of ACE2 receptors could be considered as the cause. However, the exact etiopathology underlying the chemosensitive disorders in COVID-19 infections has not been elucidated.

  Clinical manifestation Top

The clinical presentations of COVID-19 patients vary from asymptomatic carriers’ status to severe forms such as pneumonia and even respiratory failure.[22] Asymptomatic COVID-19 patients usually do not show any clinical manifestations but can transmit the infection to a similar degree as symptomatic patients.[23] The clinical features of the COVID-19 patient include lower respiratory tract illness with dry cough, fever, and dyspnea.[24] The majority of the COVID-19 patients completely recover after SARS-CoV-2 infection. However, some patients continue to present with olfactory dysfunction even after recovery from the SARS-CoV-2 infection.

Anosmia and hyposmia are the inability to perceive smells and a reduced or altered ability to smell, respectively, associated with COVID-19 infection. Olfactory dysfunction in COVID-19 patients often appears early, sudden, severe, and isolated. Olfactory dysfunction following SARS-CoV-2 infection affects the mood of the person, food enjoyment, ability to detect the dangers, general health condition, and social life.[25] Many patients also present with parosmia (distorted smell in the presence of a familiar odor source) and phantosmia (experience of smell in absence of odor sources).[26] Another study showed the equal prevalence of male and female patients with loss of sense of smell associated with SARS-CoV-2 infection.[27] However, Lee et al.[28] documented a higher prevalence of female patients with smell and taste disturbances in COVID-19 patients.

Sudden onset of olfactory dysfunction may be found in COVID-19 patients with or without other symptoms. Another study from Italy showed that impaired smell sensation was commonly found in younger patients and women.[29] In many cases, the resolution of the olfactory dysfunction occurs within 2 weeks.[29] Olfactory dysfunction and disturbances in taste sensation are often interchangeable in COVID-19 patients. SARS-CoV-2 usually targets both olfactory and gustatory systems, so many patients describe the altered taste; however, this symptom can be attributed to impaired retro-nasal olfaction (flavor) rather than impaired gestation (sweet, sour, salty, bitter). For this cause, it is thought that the chemosensory impairment is likely olfactory in the case of COVID-19 patients. In COVID-19 patients, loss of smell may be a presenting symptom before other symptoms such as cough, fever, and dyspnea. The olfactory dysfunction often affects the quality of life of the patients. Patients with olfactory dysfunction usually encounter problems during cooking, social relationships, personal hygiene, and emotional problems such as depression. The olfaction has an important role in detecting the warnings of the dangerous hazards in routine life such as gas and chemicals.[30] Post-viral smell disturbance is one of the common etiologies for olfactory loss. Based on the evidence, olfactory training (OT) is usually recommended for the management of olfactory dysfunction after viral infection.[31] Patients with sudden onset of olfactory dysfunction should be considered to be COVID-19-positive.[32] Patients with COVID-19 infection presenting with anosmia require complete head and neck examination. Anterior rhinoscopy and examination of the oral cavity must be done routinely by the clinician in the outpatient department. All patients with olfactory dysfunction require diagnostic nasal endoscopy to rule out any obstructive pathology in the nasal cavity.

  Investigations Top

Investigations should be done to differentiate between the obstructive and non-obstructive pathology causing olfactory dysfunction. The smell can be tested by University of Pennsylvania Smell Identification Test (UPSIT), which is considered as safe, being culturally dependent need proper validation in different country populations.[33] Acoustic rhinometry assessment may be used to assess the nasal cross-sectional area for assessing the nasal obstruction. In COVID-19 patients, smell and taste sensation assessment can be done by a written or online questionnaire, which is qualitative but most often lack quantitative assessment.[33] Visual analog scale (VAS) is fast and easy to perform the safe quantitative method in daily clinical practice. Either VAS and/or disposable olfactory or gustatory test is usually recommended for an appropriate and safe quantitative evaluation of the loss of smell and/or taste among COVID-19 patients. Subjective olfactometry is usually not recommended as in a face-to-face application in COVID-19 patients because of the risk of transmission to patients and healthcare professionals.[34] Chemical gustometry is a useful test to differentiate between flavor (smell in addition to taste) and pure taste disturbances, but as in the case of smell tests and because of the high risk of disease transmission, only individual disposable kits are recommended in COVID-19 patients. Diagnostic nasal endoscopy and computed tomography scans are useful investigations to find out the obstructive pathology in the nose and sinuses.[35] Magnetic resonance imaging (MRI) of the brain may show inflammation at the olfactory cleft of the COVID-19 patients with anosmia in comparison to healthy non-COVID-19 patients.[36] Functional MRI is important imaging to assess the olfactory area.

  Treatment Top

The improvement in smell disturbances or olfactory dysfunction in a short period after COVID-19 infections suggests some transient inflammation in response to SARS-CoV-2 on the nasal cavity and oral cavity epithelial cells and sensory receptor cells.[37] If the post-COVID olfactory dysfunction improves spontaneously, specific treatment may not be needed. However, if the olfactory impairment continues for more than 2 weeks, it should be reasonable to treat such a clinical problem. The efficacy of available medications in COVID-19-related olfactory dysfunction is still not known, although this treatment is potentially helpful for some extent toward olfactory dysfunction with COVID-19 infection. There are certain supportive medical treatments for post-COVID-19 olfactory dysfunction which include zinc, alpha-lipoic acid, vitamin A, minocycline, traditional Japanese medicine, theophylline, acupuncture, systemic and topical corticosteroids.[38],[39] Although there is no evidence-based use of topical steroid nasal spray for the treatment of post-COVID, oral and intranasal steroids are usually used to treat inflammatory components in patients of post-infectious olfactory dysfunction. However, oral or systemic corticosteroids are not used widely in the current COVID-19 pandemic because evidence of benefit is lacking and also with the presence of potential risk. In olfactory dysfunction, one study recommended the use of intranasal corticosteroids with the preference of spray formulation in comparison to drops or gel.[40] Mometasone furoate nasal spray accelerates the recovery rate of COVID-19 anosmia.[40] Twice daily applications of the topical corticosteroid spray are very helpful. Topical corticosteroid with squirt system is more effective in viral infection-induced olfactory dysfunction.[40] In otorhinolaryngological practice, oral steroids are usually administered in certain diseases such as idiopathic sensorineural hearing loss, facial nerve palsy, and acute post-viral anosmia. Steroid administration is usually associated with a high chance of recovery in idiopathic sensorineural hearing loss, whereas olfactory dysfunction particularly acute or reversible stages of olfactory mucosal injury may be improved with steroids.[39] Currently, OT is a recommended approach for post-COVID-19 olfactory dysfunction. OT is usually associated with minimal harmful effects and is beneficial to improve olfactory dysfunction. If OT is started early, it will provide high compliance. However, the only disadvantage is sustained daily training for months.[41] OT is a novel intervention that improves olfactory function by repeated sniffing and/or exposure to robust odors. However, the post-training improvements of olfaction are due to changes at the level of the olfactory epithelium or more centrally at the olfactory bulb, which is still unknown. OT includes repeated and deliberate sniffing of a set of odorants (e.g., lemon, rose, cloves, and eucalyptus) for 20 s each at least twice daily for at least 3 months or longer if possible. The study showed that olfaction is improved in the case of post-infectious olfactory dysfunction.[42] OT can be done in case of persistent COVID-19-related olfactory dysfunction as this therapy has low cost and nil or negligible side effects.

Approximately 90% of the COVID-19 patients with olfactory dysfunction may return to normal within the first month, and the OT is strongly suggested if the olfaction has not recovered after the first 1 month but can be started earlier. OT is a promising treatment option for olfactory dysfunction and is often successful in patients with loss of smell following respiratory tract infection.[43] However, the efficacy of the OT program has been applied in different patients with olfactory dysfunction, in which the neural basis of this treatment remains poorly understood. The olfactory system has a unique ability to be stimulated by the sensorimotor act of sniffing, which is characterized by a short and deep inhalation of breath through the nose, without the presence of odor.[44] OT is currently the only evidence-based treatment option for post-viral smell disturbances.[45]

  Conclusion Top

An intact smell sensation is needed for the human being to recognize the chemical signals from the surroundings. Any defect in the smell sensation affects the quality of life. The current research suggests that hyposmia or anosmia can be implemented as part of the screening for patients of COVID-19. COVID-19 patients often present with the symptom of sudden onset olfactory dysfunction and even isolated olfactory dysfunction. The patients with olfactory dysfunction should self-isolate before microbiological confirmation. Altered smell and taste in COVID-19 patients result in severe disruption of daily living which affects the psychological well-being and health of the patients. If the smell and taste disorders persist, it hampers the flavor perception, desire, or ability to prepare food and eat, weight gain, nutritional sufficiency, emotional well-being, professional practice, intimacy, and social bonding. The use of topical corticosteroid spray and olfactory training are important treatment options available for the treatment of smell and taste disorders in COVID-19 patients.

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