Letters20 October 2020

Loss of Smell and Taste in 2013 European Patients With Mild to Moderate COVID-19

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    Background: The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly. Commonly reported symptoms, such as fever, cough, dyspnea, fatigue, and myalgia, are nonspecific, and the lack of testing in some European countries may make the diagnosis of COVID-19 challenging. However, 2 distinctive symptoms were identified recently: loss of smell and loss of taste (1). These symptoms were not reported extensively in initial studies (2) and might help in the clinical diagnosis of COVID-19.

    Objective: To evaluate the prevalence and features of, as well as recovery from, smell dysfunction in European patients with mild to moderate COVID-19.

    Methods: From 22 March to 23 April 2020, we identified 2153 consecutive ambulatory and hospitalized patients with positive results on reverse transcriptase polymerase chain reaction (RT-PCR) testing at 18 European hospitals. Patients had mild to moderate COVID-19, defined as an infection not requiring intensive care, and those who were hospitalized were discharged during the study period. Of the 2153 patients, 2013 (93.5%) provided informed consent and participated in the study (Figure), which was approved by the ethics committee at each institution.

    Figure. Flow chart of the study.

    COVID-19 = coronavirus disease 2019; ICU = intensive care unit; RT-PCR = reverse transcriptase polymerase chain reaction.

    * The diagnostic tests of ambulatory and hospitalized patients were centralized in hospital laboratories, allowing identification of patients with positive results.

    † For hospitalized patients, physicians entered information directly on an online questionnaire; home-managed (quarantined) patients completed the questionnaire at home.

    ‡ Among the patients with total loss of smell, those who came from Hainaut, Belgium, were contacted to be included in a second study to objectively assess the olfactory disorder. The following exclusion criteria were considered: history of nasal surgery, history of head or neck trauma, history of chronic rhinosinusitis or polyposis, degenerative neurologic disease, and history of chronic loss of smell before the epidemic. Patients who did not respond to the questionnaire were excluded (n = 7).

    Using a standardized online questionnaire, we collected clinical and epidemiologic data from hospitalized patients on discharge day and from ambulatory patients after the resolution of key symptoms (such as cough, fever, dyspnea, headache, myalgia, and arthralgia) (Figure). We assessed general and otolaryngologic symptoms believed to be associated with COVID-19 (by using a 4-point scale, from 0 for no symptoms to 4 for severe symptoms). The olfactory and gustatory assessment was based on 8 questions on the smell and taste component of the National Health and Nutrition Examination Survey (3).

    Objective evaluations for olfactory dysfunction were performed in a subset of patients who reported total loss of smell at 1 of the study sites (EpiCURA Hospital, Hainaut, Belgium) at the time of the questionnaire. We used a standard olfactory identification test (Sniffin' Sticks [MediSense]) (4), in which we presented 16 scented pens to each patient to smell every 30 seconds. Patients were asked to choose the best term among 4 options to describe the aroma. The test was scored on the basis of a 16-point total. According to the results, patients were classified as normosmic (12 to 16 points), hyposmic (9 to 11 points), or anosmic (<9 points).

    Findings: Of 2013 patients, 161 (8%) were hospitalized (Figure); the remainder were ambulatory patients not previously hospitalized for COVID-19. The Table presents characteristics of our study participants. Loss of smell and headache were the most prevalent symptoms. A total of 1754 patients (87%) reported loss of smell, whereas 1136 (56%) reported taste dysfunction. Mean time from the end of the disease to the evaluation was 7.8 days (SD, 6.8); mean duration of general symptoms (excluding loss of smell and taste) was 11.5 days (SD, 6.0). Most patients had loss of smell after other general and otolaryngologic symptoms (Table). At the time of evaluation, 573 of 1754 patients regained their sense of smell, 60.9% of them between 5 and 14 days after the onset of smell loss; mean duration of olfactory dysfunction was 8.4 days (SD, 5.1). In the subset of 93 patients who were eligible to have an objective olfactory evaluation, 86 (92.5%) completed the assessment; anosmia and hyposmia were confirmed in more than half the patients (Table), but more than a third showed no objective signs of dysfunction.

    Table. Characteristics of the Study Sample*

    Taste disorder, defined as partial or total loss of the 4 taste types—salty, sweet, bitter, and sour (3)—affected 56.4% of patients. Additional aroma disorder (3) occurred in 82.5% of patients. Characteristics of patients with loss of taste and smell are shown in the Table.

    Two main categories of patients with total loss of smell were observed: those with and those without nasal obstruction (Table). No significant association was found between loss of smell and the otolaryngologic symptoms of nasal obstruction, rhinorrhea, and postnasal drip in the entire cohort or among subgroups with anosmia, hyposmia, or normosmia.

    Discussion: The prevalence of self-reported smell and taste dysfunction in our study is higher than previously reported and may be characterized by different clinical forms. Our results suggest that anosmia may not be related to nasal obstruction or inflammation. Future studies are needed to understand the pathophysiologic mechanisms underlying loss of smell and taste in COVID-19, including potential viral spread through the olfactory neuroepithelium and invasion of the olfactory bulb and central nervous system (5). Our study has limitations. Hospitalized patients were assessed at discharge, which may have biased our assessment of symptom duration. The study population was limited to patients with mild to moderate symptoms. Because patients were asked about taste and smell after they received their diagnosis, they may have been influenced by news reports of smell and taste dysfunction in COVID-19 and overreported these symptoms: Only two thirds of patients who reported olfactory symptoms and had objective olfactory testing had abnormal results. Nonetheless, these findings highlight the importance of considering loss of smell and taste in the diagnosis of mild to moderate COVID-19.

    References

    • 1. Lechien JRChiesa-Estomba CMPlace Set alCOVID-19 Task Force of YO-IFOSClinical and epidemiological characteristics of 1,420 European patients with mild-to-moderate coronavirus disease 2019. J Intern Med2020. [PMID: 32352202] doi:10.1111/joim.13089 CrossrefMedlineGoogle Scholar
    • 2. Rodriguez-Morales AJCardona-Ospina JAGutiérrez-Ocampo Eet alLatin American Network of Coronavirus Disease 2019-COVID-19 Research (LANCOVID-19).Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis2020;34:101623. [PMID: 32179124] doi:10.1016/j.tmaid.2020.101623 CrossrefMedlineGoogle Scholar
    • 3. Rawal SHoffman HJBainbridge KEet alPrevalence and risk factors of self-reported smell and taste alterations: results from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES). Chem Senses2016;41:69-76. [PMID: 26487703] doi:10.1093/chemse/bjv057 CrossrefMedlineGoogle Scholar
    • 4. Hummel TKobal GGudziol Het alNormative data for the “Sniffin' Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol2007;264:237-43. [PMID: 17021776] CrossrefMedlineGoogle Scholar
    • 5. Brann DH, Tsukahara T, Weinreb C, et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Preprint. Posted online 9 April 2020. bioRxiv. doi:10.1101/2020.03.25.009084 Google Scholar

    Comments

    Dr. Jerome R. Lechien, MD, PhD, MS14 July 2020
    Authors' Response to Dr Doukas and Kothari

    We thank Dr Doukas & Kothari for the relevant comment on our paper reporting loss of smell and taste in 2,013 European patients. They remind the usefulness of olfactory evaluation (psychophysical) at the bedside of patient to determine the presence of anosmia, hyposmia or normosmia. We totally agree with the comment of Dr Doukas and we also believe that the assessment of olfactory function has to be made through standardized olfactory testing, such as The University of Pennsylvania Smell Identification Test. The use of at least 16 pens is important regarding the interindividual variability in smell detection and the risk to get biased evaluation results if we use a little number of odors.1-3

    The importance of objective olfactory evaluations at baseline is strengthened regarding the recent data that support that the higher baseline severity of olfactory loss measured by the Sniffin-Sticks was strongly predictive of 2-month persistent loss.4

    Although the nasal procedures were discouraged at the onset of the disease, we think that the realization of nasofibroscopy before the test is important to assess the olfactory cleft permeability; the material being disinfected after the examination.

     References:

    1.Rimmer J, Hellings P, Lund VJ, et al. European position paper on diagnostic tools in rhinology. Rhinology. 2019; 57(Suppl S28):1-41. doi: 10.4193/Rhin19.410.

    2.Sonnet MH, Nguyen DT, Nguyen-Thi PL, Arous F, Jankowski R, Rumeau C. Fine-tuned evaluation of olfactory function in patients operated for nasal polyposis. Eur Arch Otorhinolaryngol. 2017; 274(7):2837-2843. doi: 10.1007/s00405-017-4580-1.

     3.Freiherr J, Gordon AR, Alden EC, Ponting AL, Hernandez MF, Boesveldt S, Lundström JN. The 40-item Monell Extended Sniffin' Sticks Identification Test (MONEX-40). J Neurosci Methods. 2012; 205(1):10-6. doi: 10.1016/j.jneumeth.2011.12.004.

    4.Lechien JR, Chiesa-Estomba CM, Beckers E, et al. Prevalence and Recovery of Olfactory Dysfunction in a Cohort of 1,363 COVID-19 Patients: A Multicenter Longitudinal Study. Preprint. DOI: 10.21203/rs.3.rs-38504/v1

     

     

     

     

    Sotirios G. Doukas, MD (1,2), Nayan Kothari, MD, MACP, FRCPE (1)21 June 2020
    The Utility of Olfactory Nerve Examination in COVID-19 Patients

    Dear Editor, There is evidence that a great percentage of patients may present with very mild symptoms and often be asymptomatic. Recently Lechien et al., in Annals of Internal Medicine, performed an epidemiologic study in 2013 COVID-19 patients, reporting that 87% of them reported a loss of smell and 56% reported taste dysfunction1. Also, objective evaluation of the olfactory nerve in a subset of patients 4-14 days after the onset of loss of smell and taste showed anosmia or hyposmia in more than half of the patients1. Other studies also support that anosmia, hyposmia, and dysgeusia have been recognized as symptoms for COVID 192. Other known conditions related to anosmia, hyposmia, and dysgeusia, include chronic neurodegenerative conditions of CNS such as dementia, and Parkinson’s disease, as well as chronic upper respiratory conditions such as chronic or acute rhinosinusitis3.

    Although other viral infections, except SARS-CoV-2, can also potentially cause dysfunction of the olfactory nerve through an unclear mechanism leading to sensorineural dysfunction, given the high prevalence of COVID 19 nowadays, acute anosmia seems to be significant finding with potentially high diagnostic value for this disease. The American Academy of otolaryngology and Head and Neck Surgery, has already established a COVID -19 anosmia reporting tool to collect valuable data. Also, the function of the olfactory nerve can easily be tested at the bedside using low-cost material such as coffee and vanilla products. Doty et al., summarized several standardized both psychophysical and electrophysiological tests that can be used in the clinic for the assessment of olfaction4.

    The University of Pennsylvania Smell Identification Test and standard olfactory identification test are inexpensive tests that can easily be used even by an inexperienced clinician to assess the olfactory threshold 1,5. However, the examination of the olfactory nerve at the bedside remains, unfortunately, a forgotten practice. In an era where bedside clinical skills have been in decline, redefining the value of physical diagnosis is a necessity. With the understanding that the pandemic will initiate changes in everyday practice, an evidence-based physical diagnosis will promote a meaningful cost-effective approach to medical practice.

    Given the existing evidence that SARS-CoV-2 can lead to temporary anosmia, hyposmia, or dysgeusia, assessment of olfaction should be highly considered as a standard of practice in patients under investigation for COVID 19. This could also potentially reveal several infected patients that might otherwise be asymptomatic serving as vectors and spreading the disease. Sincerely, Sotirios Doukas, MD Internal Medicine Resident Saint Peter’s University Hospital

    References

    1. Lechien JR, Chiesa-Estomba CM, Hans S, Barillari MR, Jouffe L, Saussez S. Loss of Smell and Taste in 2013 European Patients With Mild to Moderate COVID-19. Ann Intern Med. Published online May 26, 2020. doi:10.7326/M20-2428
    2. Vaira LA, Salzano G, Deiana G, Riu GD. Anosmia and Ageusia: Common Findings in COVID-19 Patients. The Laryngoscope. n/a(n/a). doi:10.1002/lary.28692
    3. Miwa T, Ikeda K, Ishibashi T, et al. Clinical practice guidelines for the management of olfactory dysfunction - Secondary publication. Auris Nasus Larynx. 2019;46(5):653-662. doi:10.1016/j.anl.2019.04.002
    4. Doty RL. Olfactory dysfunction and its measurement in the clinic. World J Otorhinolaryngol - Head Neck Surg. 2015;1(1):28-33. doi:10.1016/j.wjorl.2015.09.007
    5. Doty RL, Shaman P, Dann M. Development of the university of pennsylvania smell identification test: A standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32(3):489-502. doi:10.1016/0031-9384(84)90269-5