Decreased expression of nasal ACE2 may be correlated with lower prevalence of COVID-19 in children

1. In a cohort of 305 individuals, nasal epithelial ACE2 gene expression was found to significantly and linearly increase with age.

2. These results imply that the quantitative expression of nasal ACE2, a receptor that is known to play an active role in SARS-CoV-2 host entry, may be a factor in the disparities in disease prevalence in different age groups.

Evidence Rating Level: 1 (Excellent).

Study Rundown: ACE2, a receptor commonly found in nasal epithelium, may be associated with infection with SARS-CoV-2. This study examined rates of ACE2 gene expression in the nasal epithelium of 305 patients, aged 4 to 60 years, using previously collected data from swab RNA samples.  A positive association between ACE2 gene expression and age was found to exist, with children under the age of 10 having the lowest counts.  These results were unchanged, even with adjusted for sex and prior history of asthma. The preliminary results of this study suggest that the lower expression of nasal ACE2 in younger children may help to explain this population’s seemingly lower rate of SARS-CoV-2 infection. These findings were limited by a small and geographically constrained sample size.  Further, the prevalence of other potentially confounding variables such as ethnicity and medical conditions other than asthma were not examined.

Click to read the study in JAMA

Relevant Reading: Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

In-Depth [ retrospective cohort]: RNA sequencing was previously performed (2015-2018) on samples of nasal epithelium obtained from 305 patients in New York City for a prior asthma study.  This data was retrospectively analyzed in order to quantify ACE2 expression in various age groups. Of the patients in this cohort, ages ranged from 4 to 60 years; 48.9% were male, and 49.8% had a known history of asthma. Patients were stratified into groups of under 10 years old, 10-17, 18-24, and older than 25 years.  Linear regression models revealed that the quantity of ACE2 expression linearly increases with age (p = 0.01 between the <10 and 10 to 17 year old groups).  Data was adjusted for sex and asthma, and the trend remained consistent. This age-dependent expression of nasal epithelial ACE2 may explain the lower prevalence of COVID-19 in younger children compared to adults.

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