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Table 1.  Characteristics and Prevalent Symptoms of 202 Patients Positive for SARS-CoV-2
Characteristics and Prevalent Symptoms of 202 Patients Positive for SARS-CoV-2
Table 2.  Characteristics of Altered Sense of Smell or Taste in 202 Patients Positive for SARS-CoV-2
Characteristics of Altered Sense of Smell or Taste in 202 Patients Positive for SARS-CoV-2
1.
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. Published online February 24, 2020. doi:10.1001/jama.2020.2648PubMedGoogle Scholar
2.
Dubé  M, Le Coupanec  A, Wong  AHM, Rini  JM, Desforges  M, Talbot  PJ.  Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43.   J Virol. 2018;92(17):e00404-18. doi:10.1128/JVI.00404-18PubMedGoogle Scholar
3.
Sungnak  W, Huang  N, Bécavin  C, Berg  M, Network  HLB. SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways. ArXiv200306122 Q-Bio. March 13, 2020. Accessed April 6, 2020. https://arxiv.org/abs/2003.06122
4.
Giacomelli  A, Pezzati  L, Conti  F,  et al.  Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study.   Clin Infect Dis. 2020;ciaa330. Published online March 26, 2020. doi:10.1093/cid/ciaa330PubMedGoogle Scholar
5.
World Health Organization. Country and technical guidance—coronavirus disease (COVID-19). Accessed March 25, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance
6.
Hopkins  C, Gillett  S, Slack  R, Lund  VJ, Browne  JP.  Psychometric validity of the 22-item Sinonasal Outcome Test.   Clin Otolaryngol. 2009;34(5):447-454. doi:10.1111/j.1749-4486.2009.01995.xPubMedGoogle ScholarCrossref
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    1 Comment for this article
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    Loss of smell in COVID
    Amos Korczyn, MD, MSc | Tel Aviv University, Tel Aviv, Israel
    The recent paper by Spinato et al, “Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection”, claims that COVID patients frequently reported loss of both smell and taste. The loss of smell is non-specific and could result from previous nasal disease, smoking or preclinical Parkinson disease. Unfortunately, there was no control group (for example, matched group of subjects who were found to be negative for SARS-CoV-2).

    More disturbing is the statement that patients lost their sense of taste. This was based solely on patients’ reports during a telephone interview. People who lose their sense of smell
    frequently complain of loss of taste but clinical examination demonstrates intact taste.

    While loss of smell is quite likely because the nasal mucosa can be invaded by the SARS-CoV-2, there is no explanation for the reported loss of taste which is likely to be a misinterpretation by the patients.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Research Letter
    April 22, 2020

    Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection

    Author Affiliations
    • 1Section of Otorhinolaryngology, University of Padova, Treviso, Italy
    • 2Unit of Cancer Epidemiology, Aviano National Cancer Institute, IRCCS, Aviano, Italy
    • 3Section of Otorhinolaryngology, University of Padova, Padova, Italy
    • 4Guy’s and St Thomas’ Hospitals, London, United Kingdom
    JAMA. 2020;323(20):2089-2090. doi:10.1001/jama.2020.6771

    Since December 2019, a pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally.1 A spectrum of disease severity has been reported, with main symptoms that include fever, fatigue, dry cough, myalgia, and dyspnea. Previous strains of coronavirus have been demonstrated to invade the central nervous system through the olfactory neuroepithelium and propagate from within the olfactory bulb.2 Furthermore, nasal epithelial cells display the highest expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in the respiratory tree.3

    Despite anecdotal reports of anosmia, only 1 study to our knowledge has evaluated the prevalence of smell and taste disturbance in hospitalized patients with COVID-19, reporting an overall prevalence of 34% but without data on timing of onset in relation to other symptoms.4

    This study evaluated prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections.

    Methods

    The study was approved by the ethics committee of Treviso and Belluno provinces, and informed consent was obtained verbally for telephone interviews. Adults (aged ≥18 years) consecutively assessed at Treviso Regional Hospital between March 19 and March 22, 2020, were included if they tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs that were performed according to the World Health Organization recommendation5 and if they were suitable for home management as mildly symptomatic.

    Patients were contacted 5 to 6 days after the swab was performed, the demographic information was reported, and the Acute Respiratory Tract Infection Questionnaire (ARTIQ; with symptoms scored as none, 0; a little, 1; a lot, 2) was administered. During the telephone interview, they were asked whether they had experienced a sudden onset of an altered sense of smell or taste in the 2 weeks before the swab through completion of the Sino-nasal Outcome Test 22 (SNOT-22). The SNOT-22 grades symptom severity as none (0), very mild (1), mild or slight (2), moderate (3), severe (4), or as bad as it can be (5).6 Symptom prevalence was expressed as the percentage of total patients; 95% confidence intervals were calculated using the Clopper-Pearson method. Prevalence was compared using the Fisher exact test. A 2-sided P < .05 was considered statistically significant. Statistical analyses were performed using R version 3.6.

    Results

    Of 374 eligible patients, contact information was available for 283; 202 (71.4%) completed the telephone survey.

    Demographic data and clinical features are summarized in Table 1. The median age was 56 years (range, 20-89 years); 52.0% were women. Any altered sense of smell or taste was reported by 130 patients (64.4%; 95% CI, 57.3%-71.0%), with a median SNOT-22 score of 4 (interquartile range, 3-5); 23.8% reported a score of 5 (Table 2). Of 130 patients reporting an altered sense of smell or taste, 45 (34.6%) also reported blocked nose. Other frequent symptoms were fatigue (68.3%), dry or productive cough (60.4%), and fever (55.5%). Among all patients, the timing of an altered sense of smell or taste onset in relation to other symptoms occurred before other symptoms in 24 (11.9%); at same time as in 46 (22.8%); and after other symptoms in 54 (26.7%; Table 2). An altered sense of smell or taste was reported as the only symptom by 6 patients (3.0%). An altered sense of smell or taste was more frequent among 105 women (72.4%; 95% CI, 62.8%-80.7%) than among 97 men (55.7%; 95% CI, 45.2%-65.8%; P = .02).

    Discussion

    Alterations in smell or taste were frequently reported by mildly symptomatic patients with SARS-CoV-2 infection and often were the first apparent symptom. The results must be interpreted with caution due to study limitations: data were self-reported and based on a cross-sectional survey, the sample was relatively small and geographically limited, more severe patients were not included, and data regarding the subsequent course of the disease was not available. Although the SNOT-22 questionnaire has been shown to correlate with objective testing of olfactory function, patients may have difficulty in quantifying olfactory function; objective tests should be included in future studies.

    If these results are confirmed, consideration should be given to testing and self-isolation of patients with new onset of altered taste or smell during the COVID-19 pandemic.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Daniele Borsetto, MD, Guy’s Hospital, London SE1 9RT, United Kingdom (daniele.borsetto@gmail.com).

    Accepted for Publication: April 14, 2020.

    Published Online: April 22, 2020. doi:10.1001/jama.2020.6771

    Author Contributions: Drs Spinato and Boscolo-Rizzo had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Spinato, Borsetto, Hopkins, Boscolo-Rizzo.

    Acquisition, analysis, or interpretation of data: Fabbris, Polesel, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

    Drafting of the manuscript: Spinato, Fabbris, Borsetto, Boscolo-Rizzo.

    Critical revision of the manuscript for important intellectual content: Spinato, Polesel, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

    Statistical analysis: Polesel.

    Administrative, technical, or material support: Fabbris, Borsetto.

    Supervision: Spinato, Cazzador, Borsetto, Hopkins, Boscolo-Rizzo.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank Anna Menegaldo, MD, Daniele Frezza, MD, Francesca Mularoni, MD, Piergiorgio Gaudioso, MD, Silvia Marciani, MD, Samuele Frasconi, MD, Maria Ferraro, MD, Cecilia Berro, MD, and Chiara Varago, MD (University of Padova, Italy), for helping in the collection of patient data. We also thank Maria Cristina Da Mosto, MD, and Piero Nicolai, MD (University of Padova, Italy), Giancarlo Tirelli, MD (University of Trieste, Italy), Roberto Rigoli, MD (AULSS 2–Marca Trevigiana, Treviso, Italy), and Rupert Obholzer, MA(Oxon), MBBS(Lon) (Guy’s and St Thomas’ Hospitals, London, United Kingdom), for constructive criticism of the manuscript. None of these individuals received compensation for their contributions.

    References
    1.
    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. Published online February 24, 2020. doi:10.1001/jama.2020.2648PubMedGoogle Scholar
    2.
    Dubé  M, Le Coupanec  A, Wong  AHM, Rini  JM, Desforges  M, Talbot  PJ.  Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43.   J Virol. 2018;92(17):e00404-18. doi:10.1128/JVI.00404-18PubMedGoogle Scholar
    3.
    Sungnak  W, Huang  N, Bécavin  C, Berg  M, Network  HLB. SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways. ArXiv200306122 Q-Bio. March 13, 2020. Accessed April 6, 2020. https://arxiv.org/abs/2003.06122
    4.
    Giacomelli  A, Pezzati  L, Conti  F,  et al.  Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study.   Clin Infect Dis. 2020;ciaa330. Published online March 26, 2020. doi:10.1093/cid/ciaa330PubMedGoogle Scholar
    5.
    World Health Organization. Country and technical guidance—coronavirus disease (COVID-19). Accessed March 25, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance
    6.
    Hopkins  C, Gillett  S, Slack  R, Lund  VJ, Browne  JP.  Psychometric validity of the 22-item Sinonasal Outcome Test.   Clin Otolaryngol. 2009;34(5):447-454. doi:10.1111/j.1749-4486.2009.01995.xPubMedGoogle ScholarCrossref
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