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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 25
| Issue : 1 | Page : 12-17 |
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Olfactory dysfunction during the COVID-19 era: Prevalence and prognosis for recovery of sense of smell, Eastern region, Saudi Arabia
Khalid AlYahya1, Abdullah Ahmed Alarfaj1, Batool Zahar AlZahir2, Fatema Mohammed Alhelal3, Waroud Abdulaziz Al Sultan3, Ibrahim Mohammed Almulhim3, Abdullah Khalid Alhamam3
1 Otorhinolaryngology Unit, Department of Surgery, College of Medicine, King Faisal University, Hofuf, Saudi Arabia
2 Medical Intern, College of Medicine, King Faisal University, Hofuf, Saudi Arabia
3 Medical Student, College of Medicine, King Faisal University, Hofuf, Saudi Arabia
| Date of Submission | 23-Dec-2022 |
| Date of Decision | 02-Feb-2023 |
| Date of Acceptance | 05-Feb-2023 |
| Date of Web Publication | 29-Mar-2023 |
Correspondence Address:
Ms. Fatema Mohammed Alhelal
College of Medicine, King Faisal University, Hofuf
Saudi Arabia
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/sjoh.sjoh_60_22
Objective: There is a strong association between the onset of COVID-19 and olfactory dysfunction (OD) during infection or postinfection as a complication. This study is dedicated to measuring the prevalence of olfactory impairment and its clinical course among patients after COVID-19 infection. Methodology: A cross-sectional study was performed on patients with laboratory-confirmed COVID-19 infection. All participants had completed a validated questionnaire to evaluate the clinical course of OD. Results: Among the 305 participants, 138 reported sudden loss of smell. The mean time between the confirmation of COVID-19 and the onset of OD was 3.59 days. Olfactory impairment, accompanied by other symptoms prior to loss of smell, was reported in 67 participants and as an isolated disorder in 21 participants. Those affected reported nasal obstruction before loss of smell. A total of 138 participants complained of persistence of loss of smell even after the resolution of other symptoms. There is not a statistically significant relationship between the time of loss of smell relative to the confirmation of COVID-19 and the time of resolution of OD. In terms of gender, the prevalence of OD is equal among males and females, and results showed no significant relationship between them. Conclusions: The prevalence of OD is considered a complication among patients with COVID-19. The prognosis for spontaneous recovery from OD is favorable. Due to the lack of an objective measure for olfactory testing, further studies are needed to objectively measure the alteration of the smell.
Keywords: COVID-19, olfaction disorders, prevalence
How to cite this article:
AlYahya K, Alarfaj AA, AlZahir BZ, Alhelal FM, Al Sultan WA, Almulhim IM, Alhamam AK. Olfactory dysfunction during the COVID-19 era: Prevalence and prognosis for recovery of sense of smell, Eastern region, Saudi Arabia. Saudi J Otorhinolaryngol Head Neck Surg 2023;25:12-7 |
How to cite this URL:
AlYahya K, Alarfaj AA, AlZahir BZ, Alhelal FM, Al Sultan WA, Almulhim IM, Alhamam AK. Olfactory dysfunction during the COVID-19 era: Prevalence and prognosis for recovery of sense of smell, Eastern region, Saudi Arabia. Saudi J Otorhinolaryngol Head Neck Surg [serial online] 2023 [cited 2023 Jun 4];25:12-7. Available from: https://www.sjohns.org/text.asp?2023/25/1/12/372818 |
| Introduction | |  |
Olfaction and gustation are two sensory functions that are extremely important in daily life. The ability to sense odors and tastes is impaired or absent in people with smell and taste disorders. Parosmia is the perception of known and familiar odors as different stimuli.[1] Various etiologies can lead to olfactory impairment, such as viral infections that affect the upper respiratory structures and sinuses, head injuries, and aging.[1],[2] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus that attacks the lungs and other organs.[3] SARS-Cov-2 infects cells by attaching to angiotensin-converting enzyme 2 receptors, which are found in the nasal and bronchial epithelium.[4],[5] Hyposmia and hypogeusia are one of the very early symptoms of the COVID-19 virus.[6] Olfactory dysfunction (OD) has been added to the list of symptoms that may appear 2–7 days after the infection, according to the CDC (April 17, 2020). It is likely that OD could serve as a disease marker, particularly in people who are otherwise asymptomatic or have minor symptoms. The American Academy of Otolaryngology-Head and Neck Surgery has developed the COVID-19 anosmia reporting tool to allow health-care providers and patients from all over the world to report on anosmia and dysgeusia resulting from COVID-19.[7] A multicenter study was conducted in 18 European hospitals to investigate the prevalence and association of OD with disease severity. The results showed that OD is more common in mild COVID-19 forms than in moderate to critical forms. An objective olfactory evaluation was done on post-COVID patients at 6 months, which showed the disappearance of OD in 95% of patients.[8] According to a recent systematic review, 52.7% of 1627 patients had OD during the infection.[9] The percentage of OD in COVID-19 patients was 85.6% of 417 patients in Europe[10] and 68% of 59 patients in the US.[11] In a study that was conducted in Iran, 60.9% of 10,069 COVID-19 patients reported complete loss of smell.[12] In France, 41.4% of 198 confirmed COVID-19 cases reported loss of smell.[13] According to study conducted in Taif, Saudi Arabia, the prevalence of OD was 53% of 1022 COVID-19 patients.[14] Most cases of SARS-CoV-2 related OD improve spontaneously in 2 weeks. However, some cases persist beyond that.[15] Olfactory dysfunction is common among patients with COVID-19. Patients with COVID-19 may experience olfactory dysfunction along with other symptoms or experience it alone. Knowledge of olfactory dysfunction is important to reassure patients, as it is common. Diminished olfactory function can affect quality of life and cause anxiety among affected patients. In this study, our aim is to measure the prevalence and spontaneous resolution of olfactory and gustatory dysfunction and to illustrate the chronology of these dysfunctions among patients with COVID-19.
| Methodology | | |
This is a prospective cross-sectional study aimed at investigating the prevalence of OD among patients with COVID-19 whose infection was confirmed by the reverse transcription-polymerase chain reaction (RT-PCR). The study was carried out between January and October 2022 in the Eastern province of Saudi Arabia. It was conducted using a validated online questionnaire with a total of 624 respondents, of which 304 responses were accepted according to the inclusion and exclusion criteria of this study. The study was approved by the research ethics committee at our university.
Consequently, patients with a laboratory-confirmed diagnosis of COVID-19 (nasal swab RT-PCR) who experienced symptoms of OD and were from the Eastern province of Saudi Arabia were included in the study. Patients with an unconfirmed laboratory diagnosis of COVID-19 infection and patients from regions other than the Eastern province of Saudi Arabia were excluded from the study.
The study focused mainly on olfactory complications using a previously validated questionnaire adapted from a previous study conducted in University Hospital of Nancy, France[5] that was translated to Arabic. It was an online self-administered questionnaire created as a Google form, and it was distributed among COVID-19 patients in the Eastern province of Saudi Arabia through WhatsApp and E-mails. At the beginning of the questionnaire, participants were asked to give their consent and were informed about the purpose and significance of this study. The questionnaire includes a total of 24 questions and consists of two sections: (1) biographical information (age, sex, occupation, educational level, marital status, nationality, residence place, and diagnosis of COVID-19) and (2) questionnaires for the assessment of olfactory function, about the onset and course of infection, accompanying symptoms, characteristics and features of dysosmia, progression, and recovery.
Data analysis
The collected data were analyzed using the Statistical Package for the Social Sciences, software version 21 (IBM Corp., Armonk, NY, USA). The Chi-squared test was used to determine whether there is a significant difference between two categories. T-test was used to determine whether there is a significant difference between two numerical values. P <0.05 is statistically significant with a confidence level of 95%.
| Results | | |
A total of 624 completed the questionnaire, 238 were not included as they did not have COVID-19 infection. The inclusion and exclusion criteria were applied on the remaining 386, leaving only 304 patients accepted into the study. Most of the research participants were females 73.8% (225) compared to males 26.2% (79), with ages ranging from 18 to 55 years. The regional distribution of the participants was as follows: Al-Ahsa (59.5%), Dammam (27%), Khobar (5.3%), Dhahran (4.9%), Qatif (0.7%), and Jubail (0.7%). A sudden loss of smell occurred in 138 (45.4%) of the 304 COVID-19-positive participants. There was no gender difference between patients with and without OD (100 women and 38 men vs. 125 women and 41 men, P = 0.6).
The mean duration between COVID-19 infection and the appearance of loss of smell is 3.59 ± 3.404 days. 48.6% of participants experienced loss of smell after the appearance of other symptoms and 3.6% of participants had loss of smell as the initial symptom. 32.6% of the participants had loss of smell along with other symptoms at the same time and 15.2% had loss of smell as the only symptom. Almost all patients with OD (137, 99.3%) recovered their sense of smell within 21.76 ± 36.319 days [Table 1].
There was no significant relationship between the development of OD and the demographical data of the participants (age, gender, marital status, residency, and nationality). Patients with bachelor's degree are more likely to develop OD after COVID-19, P = 0.039 [Table 2]. | Table 2: Is there a relationship between demographics the presence of olfactory dysfunction?
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When investigating the relationship between demographics (gender, age, education level, occupation, marital status, residency, and nationality) and the duration between the diagnosis of COVID-19 and the appearance of OD, the statistical analysis showed no relation between them. Regarding the relationship between the duration between diagnosis of COVID-19 and OD and the disappearance of OD, there was no significant relationship (P = 0.674).
| Discussion | | |
The prevalence of OD was reported as 11.5% in a recent large epidemiological study conducted among 1104 SARS-CoV-2-positive patientsidentified through targeted tests.[16]
Regarding its reliability, OD used as a screening symptom was found to have high specificity and moderate sensitivity for the identification of COVID-19 infection.[17],[18]
Objective olfactory testing is not widely available, but rapid screening tools can facilitate the recognition of COVID-19 patients and facilitate the data collection. The olfactory assessment tool used in this study was adapted from Victor Gorzkowski et al. which consists of two sections. The first section is for biographical data and the second section is related to olfactory function assessment in COVID-19 patients.[5]
The findings of our study can be summarized as follows: A total of 624 participants completed the questionnaire. There are 238 participants who were excluded as they were not infected with COVID-19, leaving only 386 participants. According to our inclusion criteria, the age of participants should be 18 years or older and all participants should have a history of COVID-19 infection, which leaves only 304 participants is this study. Loss of smell during or after COVID-19 infection was reported by 138 out of 304 patients.
The incidence of OD and the clinical course among COVID-19 patients was systematically studied. A local cross-sectional study of 304 patients with COVID-19 in the eastern region of Saudi Arabia revealed several findings of interest. First, a significant proportion of patients with COVID-19 (45.4%) had experienced sudden olfactory impairment. Second, OD was predominant in female and married patients. In addition, patients with a bachelor's degree have significantly higher odds of developing OD after COVID-19 infection (P < 0.039). The explanation of this demographic association is not yet understood.
Although our study did not show significant relations between age groups and presenting OD, a study in Spain showed that OD presented predominantly in younger females and nonhospitalized patients.[19] A recent meta-analysis showed a pooled prevalence of 52.7% of OD among 1,627 patients with COVID-19. Patients with OD were assessed in subgroups using validated and nonvalidated instruments.[9] Studies based on validated instruments showed that the prevalence of smell loss was 86.60% compared to 36.64% in studies based on nonvalidated instruments.[9]
In terms of timing of smell loss relative to confirmation of COVID-19, results showed an average of 4 days postdiagnosis and reporting loss of smell. Another study was conducted early in the pandemic with a sample size of 23 outpatient participants and 20 inpatient participants without pneumonia. Six subjects reported altered smell a few days after diagnosis, seven subjects at the time of diagnosis, and the remaining four subjects experienced loss of smell a few days after diagnosis.[20] OD can present as isolated or in combination with other symptoms. In this study, only 3.6% of participants reported a loss of smell accompanied by other symptoms, 48.6% reported symptoms before alteration of smell, 32.6% had symptoms of COVID-19 and loss of smell at the same time, and only 21% of the participants had isolated loss of smell without any other symptoms. D'Ascanio et al. reported a coincident headache in association with the time of OD.[20]
The median time from the onset of COVID-19 symptoms and time of smell loss is 3.32 days, which is reported in 66 out of 138 patients. A similar study was done in Italy to investigate OD during acute infection and recovered patients, with a median time from the acute onset of COVID-19 symptoms to OD of 33 days and 120 days in recovered patients.[21] OD is a common sequela of COVID-19. However, the mechanism of action by which COVID-19 caused olfactory and gustatory dysfunction is not yet clear. A postviral disturbance may play a role in the pathophysiology.
Nasal obstruction prevents odors from reaching the olfactory cleft.[22] In our study, a total of 138 patients with OD also reported an association between loss of smell and nasal obstruction. Thus, this is statistically significant, which might indicate a conductive component for the symptoms. Although OD can occur in patients who do not have subjective nasal obstruction, this may indicate neural damage, as well.[23] In addition, the virus can also infiltrate the central nervous system through the olfactory bulb, or cause peripheral neuropathy, which impairs olfactory and gustatory functions.[24]
Recent studies report the efficacy of using fluticasone spray for the treatment of anosmia in patients with COVID-19. In this study, a total of 138 participants reported using corticosteroids as part of the treatment of OD. A total of 138 participants reported worsening smell loss in the following days and persistence of smell loss after the disappearance of other symptoms. Chandra et al. concluded that the use of fluticasone nasal spray and triamcinolone paste had significantly influenced the recovery of smell and taste. The study showed a significant improvement in smell and taste functions within a week after implementation of fluticasone nasal spray and triamcinolone paste. In contrast to the cases of the control group, there was either no improvement or worsening of symptoms.[25]
Olfactory training and rehabilitation play an important role in the resolution of olfactory impairment in patients with COVID-19. Frequent stimulation of olfactory neurons with different odors may enhance regeneration of the olfactory pathway. However, this method may not be effective in all patients with COVID-19. In our study, total of 138 participants who reported olfactory impairment had perceived their smell without any olfactory training.
Patients with olfactory impairment postviral infection had demonstrated a neuroinflammatory process which leads to smell alteration. Thus, by reducing this inflammation, resolution of symptoms may occur.[5] A 2021 randomized control trail aimed to test this hypothesis using the anti-inflammatory agents palmitoylethanol-amide and luteolin in a group of patients affected by persistent OD after COVID-19 to stimulate the olfactory pathway. They found that patients who receive these supplements demonstrated a good olfactory threshold, discrimination, and identification compared to the control group.[26]
A study was done in Hong Kong to investigate the OD and gustatory dysfunction among COVID-19 patients and to evaluate the association between the severity of these dysfunctions and the viral load. Interestingly, there was no association between viral load, severity, and recovery time of symptoms.[22] However, a study showed that anosmia is more prevalent among patients with less severe COVID-19.[27] There is a significant relationship between taste and smell alteration among COVID-19 patients.[22] In this study, patients with OD had associated taste disorders. 118 of 138 patients recovered taste sense, with only 20 cases of persistent taste alteration after viral infection.
In a study conducted in Europe, Lechien et al. concluded a significant association between smell and taste disorders among patients with COVID-19 (P<0.001). In their study, 417 patients with mild-moderate COVID-19 reported 85.6% and 88% olfactory and gustatory dysfunctions, respectively.[10]
In addition, a recent study found that it is possible that the phenotypic characteristics, including the incidence of OD, may differ between SARS-CoV-2 variants. There is also the possibility that the incidence of OD may vary according to ethnicity.[28]
In terms of recovery, in most cases, there is rapid recovery and in some cases, complete resolution of smell alteration, which occurs in parallel with disease activity.[29] In this study, the median time for smell recovery is 21.76 days, with a total of 137 participants reporting smell recovery and only 1 persistent case.
Study revealed the mean recovery time for olfactory and gustatory dysfunction was 10.3±8.1and 9.5±6.8days, respectively.[22] The spontaneous resolution of OD is expected to occur rapidly in most patients with COVID-19 with postviral smell loss.[27] A recent study was conducted in France to investigate the spontaneous resolution of OD, with 134 participants who had recovered from it. The mean time from the onset to the recovery period was 11.6 ± 6.2 days (range from 1 to 39 days). The recovery time occurs mostly on the 4th or 6th day after smell loss. Complete recovery was reported by 74 out of 134 patients, 62 had partial recovery, and six patients had no recovery at all. Gorzkowski et al. concluded that patients who presented without nasal obstruction symptoms showed rapid recovery compared with those who had nasal obstruction symptoms.[5] Therefore, this may support the hypothesis for a conductive system.[22]
The pathophysiology of OD is still unclear. Unfortunately, objective olfactory testing is not widely available; hence, most studies in the literature are subjective reporting of olfactory impairment. Thus, we recommend further studies to objectively assess OD among postviral infection patients.
OD is common among patients with COVID-19. Patients with COVID-19 may experience OD along with other symptoms or experience it alone. Knowledge of OD is important to reassure patients, as it is common. We encourage more studies to increase understanding of OD pathogenesis and clinical features.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Claus LE, Leland EM, Tai KY, Schlosser RJ, Kamath V, Lane AP, et al. Olfactory loss and beyond: A practical review of chemosensory dysfunction. J Am Board Fam Med 2022;35:406-19.  |
| 2. | Cavazzana A, Larsson M, Münch M, Hähner A, Hummel T. Postinfectious olfactory loss: A retrospective study on 791 patients. Laryngoscope 2018;128:10-5. |
| 3. | Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586-90. |
| 4. | Meng X, Deng Y, Dai Z, Meng Z. COVID-19 and anosmia: A review based on up-to-date knowledge. Am J Otolaryngol 2020;41:102581. |
| 5. | Gorzkowski V, Bevilacqua S, Charmillon A, Jankowski R, Gallet P, Rumeau C, et al. Evolution of olfactory disorders in COVID-19 patients. Laryngoscope 2020;130:2667-73. |
| 6. | Ciofalo A, Cavaliere C, Masieri S, Di Chicco A, Fatuzzo I, Lo Re F, et al. Long-Term subjective and objective assessment of smell and taste in COVID-19. Cells 2022;11:788. |
| 7. | |
| 8. | Lechien JR, Chiesa-Estomba CM, Beckers E, Mustin V, Ducarme M, Journe F, et al. Prevalence and 6-month recovery of olfactory dysfunction: A multicentre study of 1363 COVID-19 patients. J Intern Med 2021;290:451-61. |
| 9. | Tong JY, Wong A, Zhu D, Fastenberg JH, Tham T. The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: A systematic review and meta-analysis. Otolaryngol Head Neck Surg 2020;163:3-11. |
| 10. | Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. 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 2020;277:2251-61. |
| 11. | Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and COVID-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol 2020;10:806-13. |
| 12. | Bagheri SH, Asghari A, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Med J Islam Repub Iran 2020;34:62. |
| 13. | Tudrej B, Sebo P, Lourdaux J, Cuzin C, Floquet M, Haller DM, et al. Self-Reported loss of smell and taste in SARS-CoV-2 patients: Primary care data to guide future early detection strategies. J Gen Intern Med 2020;35:2502-4. |
| 14. | Mubaraki AA, Alrbaiai GT, Sibyani AK, Alhulayfi RM, Alzaidi RS, Almalki HS. Prevalence of anosmia among COVID-19 patients in Taif city, Kingdom of Saudi Arabia. Saudi Med J 2021;42:38-43. |
| 15. | Lisa Whitcroft K, Hummel T. Olfactory Dysfunction in COVID-19 Diagnosis and Management; 2020. Available from: https://www.cdc.gov/coronavirus/. [Last accessed on 2022 Apr 24]. |
| 16. | Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, et al. Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med 2020;382:2302-15. |
| 17. | Wee LE, Chan YF, Teo NW, Cherng BP, Thien SY, Wong HM, et al. The role of self-reported olfactory and gustatory dysfunction as a screening criterion for suspected COVID-19. Eur Arch Otorhinolaryngol 2020;277:2389-90. |
| 18. | Haehner A, Draf J, Dräger S, de With K, Hummel T. Predictive value of sudden olfactory loss in the diagnosis of COVID-19. ORL J Otorhinolaryngol Relat Spec 2020;82:175-80. |
| 19. | Izquierdo-Domínguez A, Rojas-Lechuga MJ, Chiesa-Estomba C, Calvo-Henríquez C, Ninchritz-Becerra E, Soriano-Reixach M, et al. Smell and taste dysfunction in COVID-19 is associated with younger age in ambulatory settings: A multicenter cross-sectional study. J Investig Allergol Clin Immunol 2020;30:346-57. |
| 20. | D'Ascanio L, Pandolfini M, Cingolani C, Latini G, Gradoni P, Capalbo M, et al. Olfactory dysfunction in COVID-19 patients: Prevalence and prognosis for recovering sense of smell. Otolaryngol Head Neck Surg 2021;164:82-6. |
| 21. | Pasquini J, Maremmani C, Salvadori S, Silani V, Ticozzi N. Testing olfactory dysfunction in acute and recovered COVID-19 patients: A single center study in Italy. Neurol Sci 2021;42:2183-9. |
| 22. | Cho RH, To ZW, Yeung ZW, Tso EY, Fung KS, Chau SK, et al. COVID-19 viral load in the severity of and recovery from olfactory and gustatory dysfunction. Laryngoscope 2020;130:2680-5. |
| 23. | Desforges M, Le Coupanec A, Brison E, Meessen-Pinard M, Talbot PJ. Neuroinvasive and neurotropic human respiratory coronaviruses: Potential neurovirulent agents in humans. Adv Exp Med Biol 2014;807:75-96. |
| 24. | Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun 2020;87:18-22. |
| 25. | Singh CV, Jain S, Parveen S. The outcome of fluticasone nasal spray on anosmia and triamcinolone oral paste in dysgeusia in COVID-19 patients. American Journal of Otolaryngology - Head and Neck Medicine and Surgery 2021:1;42. |
| 26. | Levy JM. Treatment recommendations for persistent smell and taste dysfunction following COVID-19-The coming deluge. JAMA Otolaryngol Head Neck Surg 2020;146:733. |
| 27. | Printza A, Constantinidis J. The role of self-reported smell and taste disorders in suspected COVID19. Eur Arch Otorhinolaryngol 2020;277:2625-30. |
| 28. | |
| 29. | Xydakis MS, Albers MW, Holbrook EH, Lyon DM, Shih RY, Frasnelli JA, et al. Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol 2021;20:753-61. |
[Table 1], [Table 2]
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