To the Editor—We read with interest the article by Wang et al [1] describing the clinical features of 69 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China. The authors provide a detailed description of major signs and symptoms of overt disease [2, 3], but fail to give an account of minor symptoms that may be present at earlier stages of the infection.

After some patients admitted for coronavirus disease 2019 (COVID-19) at the Infectious Disease Department of L. Sacco Hospital in Milan, Italy, complained of olfactory and taste disorders (OTDs), we performed a cross-sectional survey of the prevalence of these alterations in the context of SARS-CoV-2 infection. On 19 March 2020, a simple questionnaire including questions about the presence or absence of OTDs, their type and time of onset respective to hospitalization were submitted through verbal interview to all SARS-CoV-2–positive hospitalized patients who were able to give informed consent. Of 88 hospitalized patients, 59 were able to be interviewed (29 were nonrespondents, of whom 4 had dementia, 2 had a linguistic barrier, and 23 were on noninvasive ventilation) (Table 1). Of these, 20 (33.9%) reported at least 1 taste or olfactory disorder and 11 (18.6%) both. Twelve patients (20.3%) presented the symptoms before the hospital admission, whereas 8 (13.5%) experienced the symptoms during the hospital stay. Taste alterations were more frequently (91%) before hospitalization, whereas after hospitalization taste and olfactory alteration appeared with equal frequency. Females reported OTDs more frequently than males (10/19 [52.6%] vs 10/40 [25%]; P = .036). Moreover, patients with at least 1 OTD were younger than those without (median, 56 years [interquartile range {IQR}, 47–60] vs 66 [IQR, 52–77]; P = .035). All patients reported the persistence of OTDs at the time of the interview.

Table 1.

Characteristics of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Assessed for Taste and Olfactory Disorders (N = 59)

PatientsNo. (%)
Age, y, median (IQR)60 (50–74)
Male sex40 (67.8)
Days from illness onset to hospital admission, median (IQR)6 (4–10)
Days from illness onset to the interview, median (IQR)15 (10–21)
Pneumonia at hospital admission43 (72.8)
Symptoms at hospital admission
 Fever43 (72.8)
 Cough22 (37.3)
 Dyspnea15 (25.4)
 Sore throat1 (1.7)
 Arthralgia3 (5.1)
 Coryza1 (1.7)
 Headache2 (3.4)
 Asthenia1 (1.7)
 Abdominal symptoms5 (8.5)
No taste or olfactory disorders39 (66.1)
With olfactory and/or taste disorders20 (33.9)
Taste disorders only
 Dysgeusia5 (8.5)
 Ageusia1 (1.7)
Olfactory disorders only
 Hyposmia3 (5.1)
 Anosmia0 (0)
Mixed taste and olfactory disorders
 Dysgeusia and hyposmia2 (3.4)
 Dysgeusia and anosmia2 (3.4)
 Ageusia and hyposmia2 (3.4)
 Ageusia and anosmia5 (8.5)
PatientsNo. (%)
Age, y, median (IQR)60 (50–74)
Male sex40 (67.8)
Days from illness onset to hospital admission, median (IQR)6 (4–10)
Days from illness onset to the interview, median (IQR)15 (10–21)
Pneumonia at hospital admission43 (72.8)
Symptoms at hospital admission
 Fever43 (72.8)
 Cough22 (37.3)
 Dyspnea15 (25.4)
 Sore throat1 (1.7)
 Arthralgia3 (5.1)
 Coryza1 (1.7)
 Headache2 (3.4)
 Asthenia1 (1.7)
 Abdominal symptoms5 (8.5)
No taste or olfactory disorders39 (66.1)
With olfactory and/or taste disorders20 (33.9)
Taste disorders only
 Dysgeusia5 (8.5)
 Ageusia1 (1.7)
Olfactory disorders only
 Hyposmia3 (5.1)
 Anosmia0 (0)
Mixed taste and olfactory disorders
 Dysgeusia and hyposmia2 (3.4)
 Dysgeusia and anosmia2 (3.4)
 Ageusia and hyposmia2 (3.4)
 Ageusia and anosmia5 (8.5)

Data are presented as no. (%) unless otherwise indicated.

Abbreviations: IQR, interquartile range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Table 1.

Characteristics of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Assessed for Taste and Olfactory Disorders (N = 59)

PatientsNo. (%)
Age, y, median (IQR)60 (50–74)
Male sex40 (67.8)
Days from illness onset to hospital admission, median (IQR)6 (4–10)
Days from illness onset to the interview, median (IQR)15 (10–21)
Pneumonia at hospital admission43 (72.8)
Symptoms at hospital admission
 Fever43 (72.8)
 Cough22 (37.3)
 Dyspnea15 (25.4)
 Sore throat1 (1.7)
 Arthralgia3 (5.1)
 Coryza1 (1.7)
 Headache2 (3.4)
 Asthenia1 (1.7)
 Abdominal symptoms5 (8.5)
No taste or olfactory disorders39 (66.1)
With olfactory and/or taste disorders20 (33.9)
Taste disorders only
 Dysgeusia5 (8.5)
 Ageusia1 (1.7)
Olfactory disorders only
 Hyposmia3 (5.1)
 Anosmia0 (0)
Mixed taste and olfactory disorders
 Dysgeusia and hyposmia2 (3.4)
 Dysgeusia and anosmia2 (3.4)
 Ageusia and hyposmia2 (3.4)
 Ageusia and anosmia5 (8.5)
PatientsNo. (%)
Age, y, median (IQR)60 (50–74)
Male sex40 (67.8)
Days from illness onset to hospital admission, median (IQR)6 (4–10)
Days from illness onset to the interview, median (IQR)15 (10–21)
Pneumonia at hospital admission43 (72.8)
Symptoms at hospital admission
 Fever43 (72.8)
 Cough22 (37.3)
 Dyspnea15 (25.4)
 Sore throat1 (1.7)
 Arthralgia3 (5.1)
 Coryza1 (1.7)
 Headache2 (3.4)
 Asthenia1 (1.7)
 Abdominal symptoms5 (8.5)
No taste or olfactory disorders39 (66.1)
With olfactory and/or taste disorders20 (33.9)
Taste disorders only
 Dysgeusia5 (8.5)
 Ageusia1 (1.7)
Olfactory disorders only
 Hyposmia3 (5.1)
 Anosmia0 (0)
Mixed taste and olfactory disorders
 Dysgeusia and hyposmia2 (3.4)
 Dysgeusia and anosmia2 (3.4)
 Ageusia and hyposmia2 (3.4)
 Ageusia and anosmia5 (8.5)

Data are presented as no. (%) unless otherwise indicated.

Abbreviations: IQR, interquartile range; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Olfactory and taste disorders are well known to be related with a wide range of viral infections [4, 5]. SARS-CoV has demonstrated in a mice model a transneural penetration through the olfactory bulb [6]. Moreover, angiotensin-converting enzyme 2 receptor, which is used by SARS-CoV-2 to bind and penetrate into the cell, is widely expressed on the epithelial cells of the mucosa of the oral cavity [7]. These findings could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS-CoV-2 infection.

Due to limitations related to the diffusivity of the disease and emergency contingencies, it was impossible to perform a more structured questionnaire associated with validated tests (ie, Pennsylvania smell identification test) [8]. However, our survey shows that OTDs are fairly frequent in patients with SARS-CoV-2 infection and may precede the onset of full-blown clinical disease. In a pandemic context, further investigations on nonhospitalized infected patients are required to ascertain if these symptoms, albeit unspecific, may represent a clinical screening tool to orientate testing of pauci-symptomatic individuals.

Notes

Acknowledgments. The authors thank all patients enrolled in the cohort and all medical staff (paramedics, nurses, and physicians) who began this fight on one side of the wall and eventually fell ill during the battle. The authors also thank Tiziana Formenti and Bianca Ghisi for their excellent and indefatigable technical help.

Potential conflicts of interest. A. G. has received consultancy fees from Mylan and nonfinancial support from Gilead. S. R. and C. G. have received grants and fees for speaker’s bureaus, advisory boards, and continuing medical education (CME) activities from Bristol-Myers Squibb (BMS), ViiV, Merck Sharp & Dohme (MSD), AbbVie, Gilead, and Janssen. M. G. and G. R. have received grants and fees for speaker’s bureaus, advisory boards, and CME activities from BMS, ViiV, MSD, AbbVie, Gilead, Janssen, and Roche. S. A. has received support for research activities from Pfizer and MSD. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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