|Year : 2021 | Volume
| Issue : 2 | Page : 173-177
Sudden onset of olfactory and gustatory dysfunction - An early predictor to isolate the patient in COVID-19 pandemic
Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
|Date of Submission||16-Sep-2020|
|Date of Acceptance||03-May-2021|
|Date of Web Publication||31-May-2021|
Prof. Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
Source of Support: None, Conflict of Interest: None
Coronavirus disease-19 (COVID-19) is a new pandemic caused by severe acute respiratory syndrome coronavirus 2. The prevalent symptoms in COVID-19 include fever, cough, sore throat, rhinorrhea, myalgia, headache, dyspnea, and diarrhea. At the initial period of the COVID-19 pandemic, the clinical presentations such as olfactory and gustatory dysfunctions were considered as atypical. At present, olfactory and gustatory dysfunctions are not uncommon symptoms among COVID-19 infections in the COVID-19 pandemic. Initially, these two symptoms were underestimated and not recognized among scientific community. At present, many otolaryngologists over the world documented that COVID-19 patients presented with olfactory and gustatory dysfunctions even without the presence of nasal obstruction or rhinorrhea. The exact etiopathology for olfactory and gustatory dysfunctions is still not known. Future clinical and basic science studies may help to understand the mechanism for olfactory and gustatory dysfunctions in this pandemic. The objective of this review article is to discuss details of the olfactory and gustatory dysfunctions in COVID-19 patients. This article will surely increase awareness among the clinicians and people who are dealing with COVID-19 patients and their early diagnosis.
Keywords: Coronavirus disease-19, gustatory dysfunction, olfactory dysfunction, severe acute respiratory syndrome coronavirus 2
|How to cite this article:|
Swain SK. Sudden onset of olfactory and gustatory dysfunction - An early predictor to isolate the patient in COVID-19 pandemic. Indian J Health Sci Biomed Res 2021;14:173-7
|How to cite this URL:|
Swain SK. Sudden onset of olfactory and gustatory dysfunction - An early predictor to isolate the patient in COVID-19 pandemic. Indian J Health Sci Biomed Res [serial online] 2021 [cited 2021 Jul 25];14:173-7. Available from: https://www.ijournalhs.org/text.asp?2021/14/2/173/317404
| Introduction|| |
Coronavirus disease-19 (COVID-19) disease is a viral pandemic originated from Wuhan, China, and quickly spread to the whole of the world. This infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and causing thousands of death in the world. Common symptoms of the COVID-19 patients are cough, fever, myalgia, headache, rhinorrhea, sore throat, and diarrhea. Now, the global attention is mainly on the infected cases and frontline health-care workers. In current pandemic, large populations from different part of the world are presenting with flu-like symptoms, but the same quantity of testing kits are not yet reached to all. Hence, the importance is given to assess the symptoms which are the most predictive of the COVID-19 infection, and so, they can be instructed for self-isolation and stop the spreading of the disease. At present, there are few reports in media and medical literature that hyposmia or anosmia found in persons who have infected with COVID-19. Authorities from Otorhinolaryngology have warned that hyposmia or anosmia and loss of taste along with other symptoms seem to be a strong predictor of COVID-19 infection. As the research regarding the olfactory and gustatory dysfunctions in COVID-19 patients is very minimal, so this review article will definite provide a brief idea regarding these presentations as early clinical predictor.
| Methods of Medical Literature|| |
We performed a literature review of olfactory dysfunction and dysgeusia during the COVID-19 pandemic consisting the database of PubMed, Medline, Scopus, and Google scholar search with the terms COVID-19, olfactory dysfunction, and gustatory dysfunction. A search strategy using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was developed. Randomized controlled studies, observational studies, comparative studies, case series, and case reports were evaluated for the eligibility. We reviewed the 112 abstracts. This study focuses only on the sudden onset of olfactory and gustatory dysfunction. Review articles with no primary research data were also excluded. This manuscript reviews the details of clinical symptoms such as hyposmia, anosmia, and dysgeusia in COVID-19 patients. This review article presents a baseline from where further prospective study for exact etiology and pathogenesis of the olfactory dysfunction and gustatory dysfunction and helps as a spur for further research in the COVID-19 pandemic and the abnormalities in smell and taste among COVID-19 patients.
| Epidemiology|| |
The World Health Organization officially declared the COVID-19 outbreak as pandemic on March 12, 2020, where till today more than 200 countries are affected in the world. COVID-19 is a highly contagious infections of the respiratory system due to novel virus SARS-CoV-2. The first case was reported in Wuhan, China, in late December 2019 where the outbreak of the novel coronavirus now called as SARS-CoV-2 spreaded worldwide. The death percentage among 2684 positive cases of COVID-19 was around 2.84% as of January 25th, 2020, and the median age of the patients who died was 75 (age range: 48–89 years). By February 27, 2020, more than 82,000 COVID-19-positive cases and more than 2800 deaths have been documented of which around 95% of the cases and 97% of deaths were in China. By the march 26th, 2020, there were 462684 cases of the COVID-19 reported in 199 countries. Approximately 2%–3% cases in the general populations are suffered with lifelong olfactory dysfunction such as anosmia or hyposmia. Female is more commonly affected than male, and the viral upper respiratory tract infections are often seen in between the age of the fourth to eighth decades. At present, China, United States, Italy, and Spain have highest number of COVID-19 cases. One study with 7,736 cases of COVID-19 in China had not reported hyposmia in any patient. One study from Padua and Italy reported six cases of COVID-19 with only symptoms of hyposmia. COVID-19 is the largest pandemic since 1918 H1N1 influenza outbreak. Patients of COVID-19 presented with sudden presentations of olfactory and gustatory dysfunctions are helping clinicians for early suspecting the patients. These atypical clinical presentations among COVID-19 pandemic are helped to isolate the patient early.
| Coronavirus Disease-19 Virus|| |
Coronavirus includes a large family of viruses that have been considered as cause for several clinical manifestations varying from the common cold to severe clinical manifestations such as Middle East respiratory syndrome-CoV and SARS-CoV-2 which are global health concern. SARS-CoV-2 [Figure 1] is a new type of strain from this corona family which has been associated with COVID-19 infections since end of the 2019. Coronaviruses causing COVID-19 are large, encapsulated, or enveloped positive-strand RNA virus which can be classified into four genera such as alpha, beta, delta, and gamma. Out of these four types, alpha and beta are known to infect human beings. The size of the coronavirus is ranging from 60 nm to 140 nm with spike-like projection from the surface as a crown-like appearance under electron microscope, so the name coronavirus. The spikes over surface of the virus are made up of glycoprotein which act as critical for binding to the host cell receptors and play a vital role in severity of the infections of the host. The majority of the human receptors for glycoprotein of this virus, human angiotensin-converting enzyme 2 (ACE2), is seen mainly in the lower respiratory tract rather than upper respiratory tract. Hence, the scarcity of the receptors in the upper respiratory tract may cause less clinical symptoms related to upper airway. The incubation period of COVID-19 ranges from 1 to 14 days with a median of 5–6 days. A recent study documents that the incubation period may extend to 24 days. A longer incubation has implication in quarantine policies and prevention of the spread of the disease. This virus primarily transmitted through droplets but also it is seen in blood and stool, so raising question regarding mode of transmission.
|Figure 1: Structure of the COVID-19 virus (Blue arrow is spike protein over lipid membrane, red arrow indicates RNA)|
Click here to view
| Etiopathogenesis|| |
The etiopathogenesis for olfactory and gustatory dysfunctions in COVID-19 is still unknown. The two most common etiologies for olfactory dysfunctions are common cold and flu. Olfactory dysfunctions often occur after viral infections through upper respiratory tract-related common cold or influenza. Coronavirus is a family of viruses that may be associated with olfactory dysfunction. One study demonstrated that coronavirus may be found in the nasal discharge of the patients infected by coronavirus with olfactory dysfunction. However, this study found that some patients presented with normal acoustic rhinometry could not recover their olfaction, explain that inflammation of the nasal mucosa and nose block was not only causative factors for the olfactory dysfunction in this viral infection. The infections of the COVID-19 in the nasal cavity can enter into the brain through the cribriform plate near the olfactory bulb and cause olfactory dysfunction. However, anosmia or hyposmia in mild or uncomplicated cases of COVID-19 infection or in early stage of the COVID-19 need thorough assessment to rule out central nervous system involvement. One study documented that SARS-CoV-2 does not show significant nasal congestion or rhinorrhea, i.e. runny, stuffy, red, and itchy nose but with olfactory and gustatory dysfunctions. These findings suggest that a neurotropic virus which is location specific for the olfactory area. Although this virus is considered as a respiratory virus, SARS-CoV-2 is known to be neurotropic and neuroinvasive., Hence, anosmia with or without dysgeusia is manifested early in COVID-19 infections or in patients with mild or no constitutional symptoms. Inflammatory processes in the olfactory and gustatory nerves are associated with anosmia and dysgeusia, respectively. Olfactory dysfunction such as hyposmia or anosmia following upper respiratory tract infections is often called as postviral anosmia. Damage to the mucosa and central nervous system may be the probable cause for olfactory dysfunction; however, the exact etiopathogenesis is not clear. The olfactory and gustatory dysfunctions have currently been documented in patients with COVID-19 and it has been hypothesized that the nasal and oral tissues may possess the host cells for SARS-CoV-2. One study identified and documented the novel coronavirus/SARS-CoV-2 in nature on February 2020. The authors of this study documented that SARS-CoV-2 virus utilizing the same receptor, ACE2, once SARS-CoV-2 enters the cell. It has been claimed that the proportion and number of ACE2 expression cells in the nasal cavity and oral cavity tissue are comparable to the corresponding tissues in the lung and colon,, and authors wonder whether the oral and nasal tissue may be infected first by SARS-CoV-2. This result is also supported by another study that revealed that ACE2 receptors were seen on the oral mucosa particularly on the epithelial cells of the tongue. One report documented that the olfactory supporting cells, nasal respiratory cells, and stem cells express 2 genes which are involved for the transport of SARS-CoV-2 into the cell called as ACE2 and TMPRSS2, and so, these mechanisms may play a role for SARS-CoV-2 infections causing anosmia. One study from Milan, Italy documented a cross-sectional study where the prevalence of the smell disturbances and taste problems in 34% cases, 20% before, and 14% after the hospital admission. There was another report showing anosmia and ageusia as common symptoms in otherwise mild case of COVID-19 patients. Hendrik Streeck, professor in virology from German, reported that at least two-thirds of the COVID-19 patients presented with absence of smell and taste. Claire Hopkins, president of the British Association of Otorhinolaryngology, documented that the symptoms such as anosmia/hyposmia and taste disturbances have been found in patients of COVID-19 without any other classic symptoms in Italy, USA, UK, and France. Hence, these cases may act as hidden carriers and spreader of this infection and suggested for isolate these types patients for at least 7 days. Association of American Otolaryngologists has also documented that hyposmia, anosmia, and dysgeusia without other symptoms in COVID-19 patients should give rise to suspicion of the infection and isolation and testing should be considered.
| Clinical Presentations|| |
The general symptoms in COVID-19 infections are fever, cough, sore throat, myalgia, loss of appetite, diarrhea, headache, and loss of weight. The clinical presentation of COVID-19 varies from asymptomatic carriers status to the severe manifestations such as pneumonia. Asymptomatic carriers do not show any clinical symptoms but can transmit the infection in similar degrees symptomatic patients. The infection of the COVID-19 in Europe has highlighted a new type of clinical presentations such as olfactory and gustatory dysfunctions. The presence of the smell disturbance in viral infections is usually not new one in clinical practice. Virus infection in the nasal cavity may cause olfactory dysfunction by causing inflammatory reaction on the nasal mucosa and also cause rhinorrhea. Familiar viruses such as rhinovirus, parainfluenza virus, few coronavirus, and Epstein–Barr virus are associated with olfactory dysfunction. However, smell disturbances in COVID-19 infection are seen alone without associated with rhinorrhea. Postviral infections are usually common in female and middle-aged group or older individuals. The susceptibility of females to develop olfactory and gustatory dysfunctions is associated to the differences in inflammatory reaction process. Although the olfactory dysfunction is often permanent, this olfactory impairment has more favorable prognosis. Olfactory dysfunctions in COVID-19 differ from the Alzheimer's disease and Parkinson's disease where female outperforms the male.
| Olfactory Dysfunction|| |
The rapidly spread of the COVID-19 pandemic in the world highlighted that a typical clinical presentation of this disease is hyposmia or anosmia. The symptoms such as hyposmia or anosmia are not new in viral infections in the otolaryngology practice. Several viral infections are associated with olfactory dysfunction by inflammatory reaction in the nasal mucosa and associated with rhinorrhea. The common virus causing rhinorrhea and olfactory dysfunctions is rhinovirus, parainfluenza virus, Epstein–Barr virus, and few coronavirus. However, the dysfunction on olfactory function in COVID-19 infections is not associated with specifically rhinorrhea.
| Gustatory Dysfunction|| |
The different taste modalities such as sweet, salty, bitter, and sour are evaluated in the patient of COVID-19. The gustatory dysfunctions consist of the decreased or distorted ability to get the taste of the flavors. Imaging and neuropathology play an important role for detecting the abnormalities of the cranial nerves, brain, and olfactory bulb in COVID-19 patients. The neuroinvasive potential of the SARS-CoV-2 plays a vital role in the COVID-19 patients caused gustatory dysfunctions.
| Early Predictor|| |
Reverse transcription-polymerase chain reaction is considered as a recommended test for SARS-CoV-2. However, it has false negative of around 35%. The sense of smell can serve as the rapid and inexpensive diagnostic means for getting the COVID-19 cases. However, the sensitivity and specificity of the olfactory tests in COVID-19 cases under the age of 65 years would seem to be strong as the age-related reduction of the smell function occurs after the age of 65 years. Extensive study is required to assess the frequency of the anosmia/hyposmia and dysgeusia among the COVID-19 patients along with pathogenesis, duration, and role of marker of this disease progression or severity of the disease.
| Conclusion|| |
Intact smell and taste are required for the human being to recognize the chemical signals from the surroundings. Any defect in the smell and taste affects the quality of life. The present research suggests that the hyposmia or anosmia and dysgeusia can be implemented as part of the screening for patients of COVID-19. However, the suitability of these symptoms in public health settings decides on whether the symptom is seen early or only after more severe symptoms such as high fever, cough, and breathing difficulties. Hence, more studies are required to know the nature of the history of COVID-19 symptoms and order of the clinical presentations.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.
Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Swain SK, Acharya S, Sahajan N. Otorhinolaryngological manifestations in COVID-19 infections: An early indicator for isolating the positive cases. J Sci Soc 2020;47:63-8. [Full text]
Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al.
Clinical features and treatment of COVID-19 patients in Northeast Chongqing. J Med Virol 2020;92:797-806.
Vinh DB, Zhao X, Kiong KL, Guo T, Jozaghi Y, Yao C, et al
. Overview of COVID-19 testing and implications for otolaryngologists. Head & Neck 2020;42:1629-33.
Swain SK, Das S, Padhy RN. Performing tracheostomy in intensive care unit – A challenge during COVID-19 pandemic. Siriraj Med J 2020;72:436-42
Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 2020;92:441-7.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.
de Haro-Licer J, Roura-Moreno J, Vizitiu A, González-Fernández A, González-Ares JA. Long term serious olfactory loss in colds and/or flu. Acta Otorrinolaringol Esp 2013;64:331-8.
Welge-Lüssen A, Wolfensberger M. Olfactory disorders following upper respiratory tract infections. Adv Otorhinolaryngol 2006;63:125-32.
Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J, et al
. A comparative study on the clinical features of coronavirus 2019 (COVID-19) pneumonia with other pneumonias. Clin Infect Dis 2020;71:756-61.
Niklassen AS, Draf J, Huart C, Hintschich C, Bocksberger S, Trecca EM, et al
. COVID-19: Recovery from chemosensory dysfunction. A multicentre study on smell and taste. The Laryngoscope 2021;131:1095-1100.
de Wilde AH, Snijder EJ, Kikkert M, van Hemert MJ. Host factors in corona virus replication. Curr Top Microbiol Immunol 2018;419:1-42.
Richman DD, Whitley RJ, Hayden FG. Clinical Virology. 4th
ed. Washington: ASM Press; 2016.
Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, et al.
Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020;323:1406-7.
Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al.
Molecular and serological investigation of 2019-nCoV infected patients: Implication of multiple shedding routes. Emerg Microbes Infect 2020;9:386-9.
Suzuki M, Saito K, Min WP, Vladau C, Toida K, Itoh H, et al.
Identification of viruses in patients with postviral olfactory dysfunction. Laryngoscope 2007;117:272-7.
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 2020;11:995-8.
Xydakis MS, Dehgani-Mobaraki P, Holbrook EH, Geisthoff UW, Bauer C, Hautefort C, et al.
Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis 2020;20:1015-6.
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020;92:552-5.
van Riel D, Verdijk R, Kuiken T. The olfactory nerve: A shortcut for influenza and other viral diseases into the central nervous system. J Pathol 2015;235:277-87.
Lefèvre N, Corazza F, Valsamis J, Delbaere A, De Maertelaer V, Duchateau J, et al
. The number of X chromosomes influences inflammatory cytokine production following toll-like receptor stimulation. Front Immunol 2019;10:1052.
Sharer JD, Leon-Sarmiento FE, Morley JF, Weintraub D, Doty RL. Olfactory dysfunction in Parkinson's disease: Positive effect of cigarette smoking. Mov Disord 2015;30:859-62.
Hummel T, Landis BN, Hüttenbrink KB. Smell and taste disorders. GMS Curr Top Otorhinolaryngol Head Neck Surg 2011;10:Doc04.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al
. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.
Wu C, Zheng M. Single-Cell RNA Expression Profiling Shows that ACE2, the Putative Receptor of COVID-2019, has Significant Expression in nasal and Mouth Tissue, and is Co-Expressed with TMPRSS2 and Not Co-Expressed with SLC6A19 in the Tissues. Preprint. Available from: https://www.researchsquare.com/article/rs-16992/v1
. [Last accessed 2020 Mar 29].
Qi J, Zhou Y, Hua J, Zhang L, Bian J, Liu B, et al
. The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection. Int J Environmental Res Public Health 2021;18:284.
Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al.
High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020;12:8.
Brann D, Tsukahara T, Weinreb C, Logan DW, Datta SR. Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients. bioRxiv 2020;6:5801.
Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al.
Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: A cross-sectional study. Clin Infect Dis 2020;70:889-90.
Li D, Wang D, Dong J, Wang N, Huang H, Xu H, et al.
False-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2: Role of deep-learning-based CT diagnosis and insights from two cases. Korean J Radiol 2020;21:505-8.
Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: Changes with age. Science 1984;226:1441-3.