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Citation: Carlos M. Chiesa-Estomba, Jerome R. Lechien, Maria R. Barillari, Sven Saussez. Patterns of Gustatory Recovery in Patients Affected by the COVID-19 Outbreak [J].VIROLOGICA SINICA, 2020, 35(6) : 833-837.  http://dx.doi.org/10.1007/s12250-020-00272-9

Patterns of Gustatory Recovery in Patients Affected by the COVID-19 Outbreak

  • Corresponding author: Carlos M. Chiesa-Estomba, chiesaestomba86@gmail.com, ORCID: http://orcid.org/0000-0001-9454-9464
  • Received Date: 28 June 2020
    Accepted Date: 15 July 2020
    Published Date: 03 August 2020
  • Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From March 2020, several studies indicate that many subjects affected by mild-to-moderate COVID-19 presented olfactory/gustatory dysfunction (OD/GD) that appeared strongly correlated between them but not with the other symptoms suggestive of upper airway infectionIn order to evaluate patterns of gustatoy recovery, data from patients with confirmed COVID-19 were collected prospectively from 4 University Hospitals. At this relatively early point in the pandemic, the authors considered that subjective patterns of recovery of olfactory disfunction in COVID-19 patients are valuable for our patients, for hypothesis generation and treatment development.

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    1. Bhattacharyya N, Kepnes LJ (2015) Contemporary assessment of the prevalence of smell and taste problems in adults. Laryngoscope 125:1102-1106
        doi: 10.1002/lary.24999

    2. Chiesa-Estomba CM, Lechien JR, Portillo-Mazal P, Martínez F, Cuauro-Sanchez J, Calvo-Henriquez C, Saussez S (2020) Olfactory and gustatory dysfunctions in COVID-19 First reports of Latin-American ethnic patients. Am J Otolaryngol 41:102605
        doi: 10.1016/j.amjoto.2020.102605

    3. Daly BP, Daly MP, Minniti N, Daly JM (2012) Sense of taste (Effect on Behavior), encyclopedia of human behavior, 2nd edn. Academic Press, Cambridge, pp 373-378

    4. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271-280
        doi: 10.1016/j.cell.2020.02.052

    5. Hopkins C, Surda P, Kumar N (2020) Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology 58:295-298
        doi: 10.4193/Rhin20.116

    6. Lechien JR, Chiesa-Estomba CM, Place S, Van Laethem Y, Cabaraux P, Mat Q, Huet K, Plzak J, Horoi M, Hans S, Rosaria Barillari M, Cammaroto G, Fakhry N, Martiny D, Ayad T, Jouffe L, Hopkins C, Saussez S, COVID-19 Task Force of YO-IFOS (2020a) Clinical and epidemiological characteristics of 1420 European patients with mild-to-moderate coronavirus disease 2019. J Intern Med. https://doi.org/10.1111/joim.13089

    7. 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 (2020b) 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. https://doi.org/10.1007/s00405-020-05965-1
        doi: 10.1007/s00405-020-05965-1

    8. Lechien JR, Chiesa-Estomba CM, Hans S, Barillari MR, Jouffe L, Saussez S (2020c) Loss of smell and taste in 2013 European patients with mild to moderate COVID-19. Ann Int Med. https://doi.org/10.7326/M20-2428
        doi: 10.7326/M20-2428

    9. Mattos JL, Edwards C, Schlosser RJ, Hyer M, Mace JC, Smith TL, Soler ZM (2019) A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol 9:1144-1150
        doi: 10.1002/alr.22392

    10. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 82:7264-7275
        doi: 10.1128/JVI.00737-08

    11. Paderno A, Schreiber A, Grammatica A, Raffetti E, Tomasoni M, Gualtieri T, Taboni S, Zorzi S, Lombardi D, Deganello A, Redaelli De Zinis LO, Maroldi R, Mattavelli D (2020) Smell and taste alterations in COVID-19: a cross-sectional analysis of different cohorts. Int Forum Allergy Rhinol. https://doi.org/10.1002/alr.22610
        doi: 10.1002/alr.22610

    12. Shigemura N, Takai S, Hirose F, Yoshida R, Sanematsu K, Ninomiya Y (2019) Expression of renin-angiotensin system components in the taste organ of mice. Nutrients 11:2251
        doi: 10.3390/nu11092251

    13. Vaira LA, Hopkins C, Salzano G, Petrocelli M, Melis A, Cucurullo M, Ferrari M, Gagliardini L, Pipolo C, Deiana G, Fiore V, De Vito A, Turra N, Canu S, Maglio A, Serra A, Bussu F, Madeddu G, Babudieri S, Giuseppe Fois A, Pirina P, Salzano FA, De Riu P, Biglioli F, De Riu G (2020) Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study. Head Neck 42:1560-1569
        doi: 10.1002/hed.26269

    14. Yan CH, Faraji F, Prajapati DP, Ostrander BT, DeConde AS (2020) Self-reported olfactory loss associates with outpatient clinical course in Covid-19. Int Forum Allergy Rhinol 10:821-831
        doi: 10.1002/alr.22592

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    Patterns of Gustatory Recovery in Patients Affected by the COVID-19 Outbreak

      Corresponding author: Carlos M. Chiesa-Estomba, chiesaestomba86@gmail.com
    • 1. COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological
    • 2. Societies (YO-IFOS), Paris, France 2 Department of Otorhinolaryngology-Head and Neck Surgery, Osakidetza, Hospital Universitario Donostia, San Sebastian 20014, Spain
    • 3. Biodonostia Health Research Institute, San Sebastian 20014, Spain
    • 4. Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), 7000 Mons, Belgium
    • 5. Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, UFR Simone Veil, Universite' Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris 92150, France
    • 6. Department of Otorhinolaryngology and Head and Neck Surgery, CHU de Bruxelles, CHU Saint-Pierre, School of Medicine, Universite' Libre de Bruxelles, Brussels 1000, Belgium
    • 7. Department of Mental and Physical Health and Preventive Medicine, "L. Vanvitelli" University, 80138 Naples, Italy
    • 8. Department of Head and Neck Surgery, EpiCURA Hospital, Hornu 7331, Belgium

    Abstract: Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From March 2020, several studies indicate that many subjects affected by mild-to-moderate COVID-19 presented olfactory/gustatory dysfunction (OD/GD) that appeared strongly correlated between them but not with the other symptoms suggestive of upper airway infectionIn order to evaluate patterns of gustatoy recovery, data from patients with confirmed COVID-19 were collected prospectively from 4 University Hospitals. At this relatively early point in the pandemic, the authors considered that subjective patterns of recovery of olfactory disfunction in COVID-19 patients are valuable for our patients, for hypothesis generation and treatment development.

    • Dear Editor,

      Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From March 2020, several studies indicate that many subjects affected by mild-to-moderate COVID-19 presented olfactory/gustatory dysfunction (OD/GD) that appeared strongly correlated between them but not with the other symptoms suggestive of upper airway infection (Lechien et al. 2020a, b ; Hopkins et al. 2020; Paderno et al. 2020).

      Isolated OD and GD, without any other general or otolaryngologycal complaints like rhinorrhea or nasal obstruction, were also described as the main or unique symptoms of the infection in a variable percentage of cases; these patients, not initially identified as infected, could have represented a potential way to rapidly spread the infection among the population (Lechien et al. 2020b; Vaira et al. 2020).

      Post-viral gustatory dysfunction is well established, has been shown to be a key symptom of the coronavirus diseases 2019 (COVID-19), with more than 50% European and U.S mild to moderate patients reporting some degree of loss of taste (Hopkins et al. 2020; Lechien et al. 2020b; Yan et al. 2020). We have apparently overcome the worst part of the initial outbreak. However, persistent GD appears to be commonplace and will drive the demand for general practitioner, otolaryngology or neurology consultation in the next months—evidence regarding recovery will be essential in counselling our patients.

      In order to evaluate patterns of gustatory recovery, data from patients with confirmed mild COVID-19 were collected prospectively from four university hospitals. Inclusion and exclusion criteria were described in Fig. 1. All patients had at least 30-days of follow-up after their last negative subsequent COVID-19 test. Information was collected using an online questionnaire created with Professional Survey Monkey (San Mateo, California, USA). Informed consent was obtained. Data may be available upon a reasonable request and an approval from the originating university hospitals.

      Figure 1.  Gustatory dysfunction flowchart. * Those patients with symptom duration < 14 days were tested with a nasopharyngeal swab; in the case of three negative RT-PCR or patients with symptoms for ≥ 14 days, serology testing was performed.

      Relevant epidemiological and clinical features contained within the questionnaire were collected by the COVID-19 Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies (YO-IFOS), and consisted of four subsets (demographic data, medical background, ENT symptoms and olfactory and gustatory dysfunction). All patients completed the Short version of Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS) (Mattos et al. 2019). The remaining olfactory and taste questions were based on the smell and taste component of the National Health and Nutrition Examination Survey (Bhattacharyya and Kepnes 2015). Physical examination (rhinoscopy, nasal endoscopy or objective olfactory or gustatory testing) was not performed in this study due to the risk of nosocomial infection.

      Statistical Package for the Social Sciences for Windows (SPSS version 21, 0; IBM Corp, Armonk, NY, USA) was used to perform the statistical analyses. The potential associations between epidemiological, clinical and gustatory outcomes have been assessed through cross-tab generation between two variables (binary or categorical variables) and Chi square test. Incomplete responses were excluded from analysis. A level of P < 0.05 was used to determine statistical significance. A multivariate analysis (MA) was performed to address possible confounders. Part of this data was previously published in other papers (Lechien et al. 2020a, b, c ; Chiesa-Estomba et al. 2020).

      All told, 1043 patients identified in the emergency room or primary care consultation were invited and agreed to participate in the study. Among them 718 (68.8%) described a GD. 701 patients completed the study (Fig. 1). The mean age of patients was 40 ± 13 (range: 18-78). There were 471 females and 230 males. Patients were grouped according the presence or absence of olfactory dysfunction. Both groups were comparable according to age, sex ratio, comorbidities and addiction (P = 0.273, Wilcoxon). Of those patients who reported GD, there were 649 patients (92.6%) who subjectively report a partial or total loss of smell. By contrast, 52 (7.4%) did not report OD. About general symptoms, headache, cough and fever were the most common in those patients who develop a GD. After a mean follow-up of 63 ± 9 days (range: 60-76) from the first consultation, 66 (9.4%) of patients still reported a persistent subjective GD and 635 (90.6%) reported complete recovery. There was a statistical correlation between GD and OD (P = 0.001). However, no difference in the rate of gustatory recovery according to the presence or absence of olfactory dysfunction was encountered (P = 0.952). The mean duration of the GD was 11 ± 5 days (range: 3-36) in those patients who recovered (Fig. 1). There was no significant association between comorbidities and the development or persistence of GD. Other possible confounders rather than OD were identified according to our MA (Table 1).

      Characteristics All patients = 701 % P M.A.
      Median age (Years) 40 ± 13 (range: 18–78).
        Sex 0.001 0.003
        Male 230 32.8
        Female 471 67.2
      Ethnicity 0.791 0.346
        European 558 79.6
        Latin-American 136 19.4
        North American 2 0.3
        North-African 2 0.3
        Sub-Saharan African 2 0.3
      Current Smoker 83 11.8 0.334 0.291
      History of seasonal allergy 121 17.2 0.276 0.301
      Comorbidities
        Diabetes 18 2.6 0.271 0.683
        Heart problems 15 2.1 0.555 0.511
        COPD 6 0.9 0.767 0.871
        Hypertension 47 6.7 0.654 0.391
        Asthma 41 5.8 0.433 0.213
        Hypothyroidism 44 6.3 0.267 0.379
        Autoimmune disease (LES, RA) 27 3.9 0.301 0.411
      General symptoms
        Headache 539 72.6 0.001 0.009
        Myalgia 494 66.6 0.411 0.395
        Cough 373 51 0.062 0.008
        Loss of appetite 418 56.6 0.598 0.541
        Dyspnea 39 5.8 0.911 0.934
        Diarrhea, Abdominal pain 281 39.3 0.466 0.093
        Fever (> 38C) 261 36.2 0.051 0.035
        Arthralgia 359 49.5 0.467 0.402
        Nausea, vomiting 140 19.7 0.541 0.387
        Sticky mucus/phlegm 121 17.3 0.219 0.314
      Ear, nose and throat Symptoms
        Nasal obstruction 108 15.4 0.413 0.367
        Olfactory dysfunction 649 92.6 0.001 0.001
        Sore throat 189 26.2 0.404 0.635
        Rhinorrhea 79 12.5 0.433 0.391
        Postnasal drip 90 13.4 0.212 0.566
        Face pain/heaviness 103 16.6 0.133 0.418
        Ear pain 30 4.1 0.871 0.793
        Dysphagia 64 9.2 0.398 0.501
      Abbreviations: MA: multivariate analysis; SEL: systemic lupus; RA: Rheumatoid arthritis.

      Table 1.  Demographic and clinical data.

      Taste sense correspond to an integrative experience that involves the correlation of information from oral cavity mucosal surfaces through numerous peripheral cranial nerves and other sensory modalities, such as olfaction and somatosensation (Daly et al. 2012). The prevalence of self-reported gustatory dysfunction in our study was similar to those previously reported in COVID-19 patients (Lechien et al. 2020a, b ; Hopkins et al. 2020; Paderno et al. 2020; Vaira et al. 2020). However, the frequency of residual GD after 60 days of follow-up was significantly low. According to our results and similarly to previous report, GD is related to OD. Despite the rate of recovery was higher in those patients without OD, we were not able to find statistical differences among groups. According to our findings, we consider highlighting the presence of isolated GD in at least 7% of our patients.

      At this moment, the molecular mechanisms of GD in COVID-19 patients remain still unclear. Regarding taste, it depends on the activity of specialized epithelial cells and taste cells, which are located mainly in the tongue mucosa. Shigemura et al. recently found that renin-angiotensin system (RAS) components as well as angiotensin-converting enzyme- 2 (ACE-2) are expressed in mouse taste organs and are present in the taste buds of fungiform and circumvallate papillae with ENaC (epithelial sodium channel -subunit, a salt taste receptor) or T1R3 (taste receptor type 1 member 3, a sweet taste receptor component). These preliminary results indicate the existence of a local RAS in the taste organ and suggest that taste function may be regulated by both locally-produced and circulating angiotensin II (Shigemura et al. 2019).

      It is well known that SARS-CoV-2 binds directly to the ACE2 cell receptors to infect humans and it has been reported that ACE2 is the main host cell receptor of SARS-CoV-2, playing a crucial role in the entry of virus inside the cell to cause the final infection (Hoffmann et al. 2020). ACE2 receptors were also identified in brain and have been detected over glial cells and neurons (Netland et al. 2008). However, more evidence is necessary to elucidate the real mechanism for the GD.

      Limitations of this study are the exclusion of patients with severe disease, the small proportion of older patients, the higher proportion of female respondents, loss to follow-up and recruitment from ENT-Clinics, potentially introducing a selection bias. Lack of objective testing to confirm GD is also a limitation. Also, the fact that retro-olfaction is essential for taste. However, at this relatively early point in the pandemic, subjective patterns of recovery of GD in COVID-19 patients are valuable for our patients, hypothesis generation and treatment development.

    • The authors declare that they have no conflict of interest.

    • Four ethics committees approved the current study protocol (HAP2020-011; CHUSP2003 2020; EpiCURA-2020-2303; CHU-Charleroi:B3252 2020).

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