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Age-Dependent Sensory Impairment in COVID-19 Infection and its Correlation with ACE2 Expression

Somekh, Ido MD*,†; Yakub Hanna, Husam MD†,‡; Heller, Eli MD§; Bibi, Haim MD†,‡; Somekh, Eli MD†,‡

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The Pediatric Infectious Disease Journal: September 2020 - Volume 39 - Issue 9 - p e270-e272
doi: 10.1097/INF.0000000000002817
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The coronavirus disease 2019 (COVID-19) pandemic has affected people of all ages. Initial reports were mainly in adults.1 Subsequent reports confirmed contraction of the disease by children, although in lower frequencies and with milder clinical manifestations.2 Most infected persons initially manifest with nonspecific symptoms of a common viral disease (eg, fever, myalgia, cough, vomiting). However, a unique symptom that has been commonly described in persons testing positive for COVID-19 is a temporary dysfunction in taste and smell, which has been reported in 49%–70% of infected persons.3,4 Recognizing this impairment can alert individuals who lack additional symptoms, thereby leading to screening and preventing further distribution. Interestingly, discrepancies in the prevalence rates of olfactory and gustatory symptoms between European and East Asian cohorts have been reported.3–6 Increased expression of angiotensin-converting enzyme 2 (ACE2) in European populations was suggested as a possible explanation. We analyzed sensory impairment in children and adults who tested positive for COVID-19, from the city of Bnei Brak in the center of Israel, during April 2020. Bnei Brak, one of the most crowded cities in the world and the city with the highest number of children per family in Israel, has been one of the main epicenters of COVID-19 infection in Israel. We correlated our findings with recent data regarding nasal epithelial ACE2 expression in corresponding age groups to examine whether alterations in ACE2 expression may explain differential sensory impairment.


We evaluated sensory function in households in an outpatient setting in Bnei Brak, Israel, during an outbreak of COVID-19. COVID-19 was confirmed in all the participating individuals by documentation of SARS-CoV-2-positive polymerase chain reaction. Children (5–17 years of age; further divided to 5–10 and 11–17 years) and adults (18 years and older; further divided to 18–25 years and 26 and older) were evaluated for sensory impairment by responses to questions regarding the presence or lack of olfactory and gustatory dysfunction. A scoring system of 0–2 was attributed to each sense: smell and taste. Accordingly, 0 represented no loss of sense (taste or smell), 1 mild loss, and 2 complete loss, for a total score per individual of 0–4. Finally, scores of sensory impairment in the 4 age groups were correlated with published results of ACE2 expression in persons infected with COVID-19 of corresponding age groups.7 Logarithmic values of relative expression of ACE2 according to age group were converted to actual numbers. Plots comparing sensory impairment (Fig. 1A) and ACE2 expression (Fig. 1B) in the 4 age groups were correlated. The study was approved by the ethics committee at the Mayanei Hayeshua Medical Center. Statistical evaluation was performed using the t test, chi square test, and the Pearson correlation test.

Fig. 1.
Fig. 1.:
Correlation between clinical scores and ACE2 expression. A: Taste and smell impairment scores according to age groups (scoring of 0–2 was attributed to each sense: smell and taste: 0 indicates no loss of sense, 1, mild loss, and 2, complete loss). B: Relative expression of ACE2 in nasal epithelium among the different age groups (based and inferred from data reported by Bunyavanich et al). For calculation of relative expression, logarithmic values were converted to actual numbers. Correlation between A and B sets of points: 0.95 (Pearson’s correlation coefficient, P = 0.05).


Sensory Impairment

Members of 20 families were evaluated. Of the 73 respondents (mean 3.7 per family), 31 were 5–17 years of age and 42 were 18 years and older (Table 1). In total, 37 (51%) reported having some impairment of taste or smell. This included 25.8% of the children and 71.4% of the adults (P = 0.00014; risk ratio, 0.39, 95% confidence interval, 0.23–0.65). The mean score (±SD) for the pediatric respondents was 0.55 ± 1.03 and for the adults was 2.01 ± 1.66 (P < 0.0001). Stratifying the adult group by age showed a mean score of 1.25 ± 1.54 for the young adults (18–25 years of age) compared with 2.43 ± 1.61 for the older adults (P = 0.038). Stratifying the pediatric group by age revealed no reports on altered sense of taste and smell in children of age 5–10 years, compared with an average score of 0.85 ± 1.18 in children of age 11–17 years (P = 0.005).

Table 1.
Table 1.:
Characterization of Sensory Dysfunction in Persons with COVID-19, by Age

Correlation with ACE2 Expression

The mean scores of sensory impairment for the 4 age groups were correlated with published data7 of expression of ACE2 in the corresponding age groups. The correlation between the 2 sets of values (sensory impairment scores and relative ACE2 expression) was 0.95 (P = 0.05; Fig. 1).


One of the proposed mechanisms of COVID-19-related altered smell and taste is the ability of SARS-CoV-2 to bind to ACE2 at the nasal and oral mucosa. ACE2 expression in the oral cavity was even considered a gateway to infection and as an indication that the oral infection may be a possible root of SARS-CoV-2 penetration.8 Therefore, since ageusia/dysgeusia during COVID-19 infection may represent the local expression of ACE2 and, hence, the ability of oral and nasal mucosa to facilitate SARS-CoV-2 infection and its penetration, we aimed to examine the difference in impairment of sensation in the different age groups.

Among persons who tested positive for COVID-19, sensory sensation was significantly less impaired in children than in adults. This trend was even more explicit in a comparison of younger children (of age 5–10 years), none of whom had sensory impairment, with their parents. Sensory impairment was significantly higher among adults of >25 years of age than among younger adults. The stepwise increase in taste and smell impairment with increased age suggests that the lower rates in children are not due to reporting bias but may reflect real differences. To avoid cultural, ethnic and reporting biases, the study was focused on families from a homogenous population and compared adults and children residing in the same households. The significant difference in sensory impairment between children and adults, and particularly between younger children and middle-age adults, corroborate data that showed age-dependent expression of ACE2 in nasal epithelium, in similar age groups as in the current study.7 This supports the possibility that the distribution and expression of ACE2 in the oral cavity and in nasal epithelium could contribute to differences in sensory impairment.

Our data also offer a possible explanation for the tendency among children to milder symptoms of COVID-19 illness despite their having higher nasopharyngeal viral loads at presentation.9 Presumably, the decreased availability of ACE2 receptors in the naso-pharynx of infants and children prevents profound sensory impairment as well as severe illness, despite higher viral loads. The findings of reduced rates of infection in children compared with adults in the same households10 are also in line with our findings. We suspect that the reduced susceptibility of children to sensory impairment may reflect reduced susceptibility to COVID-19 infection of other target organs in the pediatric population to the insults incurred by SARS-CoV-2. Our results may serve as a paradigm for the milder clinical phenotype of COVID-19 observed in children.


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10. Somekh E, Gleyzer A, Heller E, et al. The role of children in the dynamics of intra family coronavirus 2019 spread in densely populated area [published online ahead of print, 2020 Jun 1]. Pediatr Infect Dis J. 2020.

COVID-19; SARS-CoV-2; taste; smell; ACE2

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