i. A statement with potential conflict of interests related to
the manuscript content.
Conflict of interest : all authors declare no conflict on
interests related to this manuscript.
ii. Financial support.
Financial support : none
iii. Abstract and keywords.
No abstract provided.
Keywords: COVID-19, olfactory dysfunction, gustatory dysfunction,
anosmia, ageusia, children, paediatric population.
iv. Main text.To the Editor:
Olfactory and gustatory dysfunctions (OGD) have been reported as
relevant symptoms that may predict presence of coronavirus disease 2019
(COVID-19) in adults, associated with mild or moderate
disease1, 2, 3. However, published data on OGD in
children are scant, likely due to several factors specific to the
pediatric population such as a lower incidence of infection, the
tendency of COVID-19 to be asymptomatic4, 5, and the
difficulty of studying childhood OGD with objective methods. Two case
reports have been published to date: one with 3
adolescents6, and the other describing a 17-year-old
girl with beta-thalassemia who presented total loss of smell and taste
for 8 days7. Current data on the prevalence of OGD are
based on only 2 small cohorts of COVID-19–positive
children8, 9. In a related study, Mannheim et
al.10 describe that 19 (30%) of 64 infected children
(0–17 years old) presented nasal congestion, rhinorrhea, and total loss
of smell, though providing no data on the exact number of patients with
olfactory dysfunction exclusively.
The present study aimed to evaluate OGD among symptomatic COVID-19
children presenting to a referral pediatric hospital for this disease in
Madrid, Spain. The database of positive SARS-CoV-2–RT-PCR (reverse
transcription-polymerase chain reaction) cases diagnosed between March
20 and July 13, 2020 was retrospectively reviewed. Demographic
information, COVID-19 symptoms, disease severity and clinical course,
comorbidities, and blood biomarkers were obtained from electronic
medical records. Information on smell and taste disorders and any
incomplete data on other COVID-19 symptoms was obtained by telephone
interview with parents and patients, who provided oral consent. COVID-19
severity was established according to the classification by
Qiu9. Questionnaire data on onset, duration of smell
and taste disorders was used, and severity was classified according to a
scale modified from Izquierdo-Dominguez et al. 1 Based
on the degree of smell or taste loss, we stratified patients as
normosmic-mild (0–3 points), moderate (4–6 points), or severe loss
(7–10 points).
Qualitative variables are expressed as numbers and percentages, and the
Chi-square test was used for comparison. Quantitative variables appear
as mean and standard deviation or median and interquartile range (IQR)
according to their distribution. Normality of age distribution was
confirmed by the Shapiro-Wilk test. ANOVA test and the DMS as post hoc
test were used to compare normally distributed variables. Statistical
significance was set at 95% (p < 0.05).
Ninety-two children were identified as SARS-CoV-2–RT-PCR positive; 2
declined to participate. Asymptomatic patients were excluded. Fifty
patients were diagnosed with symptomatic COVID-19 (52% male; mean age:
7±7 years, IQR: 6 months–12 years). Patients under 6 years of age
(n=20) were excluded for potential poor reliability on self-reported
smell function. Thirty patients were finally enrolled
(Figure 1). Seven (23.3%) patients
presented mild COVID-19, 11 (36%) were moderate cases, and 12 (40%)
had severe disease. Nineteen (63.33%) required hospitalization, and
11(36.6%) were discharged after emergency department evaluation.
A total of 8 (26.6%) (range 9–17 years of age) of 30 symptomatic
children presented OGD; they were older than the children without OGD
(12.6 ± 2.7 years vs. 10.6 ± 3.1 years, respectively; p=0.045). Five
(16.6%) of 30 COVID-19–positive children presented both smell and
taste disorders and 3 (10%) had gustatory dysfunction only (Figure 1).
OGD was severe in all patients (7–10 points) (Tables 1 and 2).
OGD onset was sudden in all patients; 6 developed symptoms
simultaneously with the other COVID-19 symptoms, and 2 (25%) before
other disease manifestations. Of the latter, one developed both
symptoms, and the other only gustatory dysfunction (Table 2). In no case
did OGD appear as the only symptom. OGD was transient in all patients,
[median olfactory dysfunction duration, 45 days (range 15–120 days),
and median gustatory dysfunction of 10 days (5–120 days)] (Table 1).
There was no significant difference in the prevalence of OGD with
respect to the severity of COVID-19 (mild 4.3%, moderate 36.4%, severe
25%) nor in COVID-19 severity between patients with and without OGD
(Table 1) (p=0.578). Five patients with OGD (62.5%) were hospitalized
(2 in the intensive care unit). Seven subjects presented digestive
symptoms, 6 had fever (>37.8ºC), 4 cutaneous
manifestations, 3 pneumonia, 2 odynophagia, and 1 dyspnea. All patients
recovered without sequelae except for one asthmatic patient with
exercise-induced dyspnea (case 4) (Table 2). Inflammatory markers are
described in Table 1.
The prevalence of OGD in this cohort was 26.6%, a much lower rate than
that reported in adults1, 2, 3, including the European
multicenter study by Lechien et al.3 in which 85.6%
and 88.0% of COVID-19 patients reported olfactory and gustatory
dysfunctions, respectively, as well as a Spanish study in which 53.7%
and 52.2% of patients presented severe smell or taste loss,
respectively1. Furthermore, the prevalence of OGD in
our study is somewhat lower than in the multicenter Qui et al.
study9, which included 27 children (6–17 years old),
with 10 of 27 (37%) subjects (15–17 years of age) presenting OGD. In
contrast, Erdede et al.8 detected a lower prevalence
(3.7%) than ours, reporting only 1 child with taste loss among 27
COVID-19–positive children.
In our study, 10% of patients had isolated gustatory dysfunction, an
uncommon but previously reported feature in adults3and children8. The degree of OGD has not been
previously described in the pediatric population, and according to our
findings, all subjects experienced a severe symptomatic form.
Our patients with OGD were somewhat younger than in the study by Qui et
al.9 (12.6 ± 2.7 years vs. 16.6 ± 0.7, respectively);
in our population, however, children who developed OGD were older than
those who did not. This could be explained by a lesser susceptibility to
OGD among younger children or lower diagnostic accuracy. Our patients
seemed to have more severe COVID-19 than in other reports in
pediatric9 and adult subjects1, 3.
However, the severity in patients with OGD was not significantly
different than OGD-free individuals, nor among patients with OGD,
although our limited sample size is a potential source of bias.
As described by Qiu et al.10, OGD onset coincided with
other symptoms in most patients, thus preventing its use as an early
sign of COVID-19 in children. The duration of OGD was between 5 and 120
days, which is longer than that reported by Mak et
al.6 (3->13 days), possibly due to a
longer follow-up in our study. Interestingly, loss of smell resolved
before loss of taste in our cohort.
The limitations of this study include the potential bias from selecting
a population treated in a tertiary hospital, which may not reflect the
entire spectrum of COVID-19 in children, particularly mild forms.
Further limitations are the retrospective study design and the lack of
an objective, validated method to assess OGD.
In summary, this is one of the few reports in Europe describing OGD in
children with COVID-19. In the pediatric population with predominantly
moderate to severe COVID-19 presented here, OGD displayed a low
prevalence, was not an early sign of disease onset, and tended toward a
severe and long-lasting course.