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New Study Finds Potential Reason Why COVID-19 Occurs Less In Children
by
Tyler Durden
Wed, 08/12/2020 - 06:00
Authored by Paula Liu via The Epoch Times,
The reason COVID-19 occurs less frequently in children could be due to the lack of a certain enzyme, researchers have found.
This
new study detailed in the Journal of the American Medical Association (JAMA) on May 20, discovered that
the angiotensin-converting enzyme 2 (ACE2), which grows in abundance as the individual grows, might be the reason that less than two percent of all individuals infected with SARS-CoV-2 - the virus that causes the COVID-19 disease - are children.
Researchers had suspected that COVID-19 susceptibility could be linked to the amount of gene expression of ACE2 seen in the nasal cavity, given that the
enzyme acts as a receptor to allow the SARS-CoV-2 virus to pass into the body.
To investigate this potential link, researchers looked for a relationship between the two - the level of gene expression of ACE2 in the nose and COVID-19 infection - by taking nasal swabs from 305 people involved in an asthma
study. Researchers hypothesized that the lower the levels of enzyme gene expression, the less likely it is a person will be infected by COVID-19.
Researchers said they chose to swab the nose because it is one of the first access points for SARS-CoV-2 to infect an individual.
Samples were taken from both asthmatic (49.8 percent) and non-asthmatic patients. The 305 people involved in the study were between four to 60 years of age.
Researchers said they found a clear association between ACE2 expression and age - opening up a possible explanation as to why most children, who tend to have lower levels of enzyme expression, are less susceptible to COVID-19.
Supinda Bunyavanich, professor of Genetics and Genomic Sciences and Paediatrics at Mount Sinai, said in a
press release that the study found “that there are low levels of ACE2 expression in the nasal passages of younger children, and this ACE2 level increases with age into adulthood.
“This might explain why children have been largely spared in the pandemic,” Bunyavanich said.
Here's a link to that study published in Jama:
This study compares angiotensin-converting enzyme 2 (ACE2) gene expression, which has been associated with SARS-CoV-2 cell entry, in the nasal epithelium of children vs adults.
jamanetwork.com
May 20, 2020
Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults
Supinda Bunyavanich, MD, MPH1;
Anh Do, PhD2;
Alfin Vicencio, MD1
Author Affiliations
Article Information
JAMA. 2020;323(23):2427-2429. doi:10.1001/jama.2020.8707
COVID-19 Resource Center
Children account for less than 2% of identified cases of coronavirus disease 2019 (COVID-19).
1,
2 It is hypothesized that the lower risk among children is due to differential expression of angiotensin-converting enzyme 2 (ACE2),
3 the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for host entry.
4 We investigated
ACE2 gene expression in the nasal epithelium of children and adults.
Methods
We conducted a retrospective examination of nasal epithelium from individuals aged 4 to 60 years encountered within the Mount Sinai Health System, New York, New York, during 2015-2018. Samples were collected from individuals with and without asthma for research on nasal biomarkers of asthma. The study was approved by the Mount Sinai institutional review board. Written informed consent was obtained from participants (or their parents for minors). Nasal epithelium was collected using a cytology brush that was immediately placed in RNA stabilization fluid and stored at −80 °C. RNA was isolated within 6 months. RNA samples were checked for quality and sequenced as a single batch in 2018. Sequence data processing included sequence alignment and normalization of gene expression counts across genes and samples.
Given the role of ACE2 in SARS-CoV-2 host entry,
4 ACE2 gene expression was the focus of this study. Linear regression models with and without adjustment for covariates (sex and asthma) were built with
ACE2 gene expression in log2 counts per million as the dependent variable and age group as the independent variable using R software, version 3.6.0 (R Foundation). Age was categorized into the following groups reflecting developmental life stages: younger children (aged <10 years), older children (aged 10-17 years), young adults (aged 18-24 years), and adults (aged ≥25 years). Two-sided tests and a significance threshold of
P ≤ .05 were used. Trend pattern was evaluated using polynomial orthogonal contrasts.
Results
The cohort of 305 individuals aged 4 to 60 years was balanced with regard to sex (48.9% male). Because the cohort had been recruited to study biomarkers of asthma, 49.8% had asthma.
We found age-dependent
ACE2 gene expression in nasal epithelium (
Figure).
ACE2 gene expression was lowest (mean log2 counts per million, 2.40; 95% CI, 2.07-2.72) in younger children (n = 45) and increased with age, with mean log2 counts per million of 2.77 (95% CI, 2.64-2.90) for older children (n = 185), 3.02 (95% CI, 2.78-3.26) for young adults (n = 46), and 3.09 (95% CI, 2.83-3.35) for adults (n = 29).
Linear regression with
ACE2 gene expression as the dependent variable and age group as the independent variable showed that compared with younger children,
ACE2 gene expression was significantly higher in older children (
P = .01), young adults (
P < .001), and adults (
P = .001) (
Figure). As the distributions of sex and asthma varied among the age groups, a linear regression model adjusted for sex and asthma was built that also showed significant adjusted associations (
P ≤ .05) between
ACE2 expression and age group. Regression (β) coefficients for age groups from the unadjusted and adjusted models are shown in the
Table. These regression coefficients indicate the difference in
ACE2 expression (in log2 counts per million) between a given age group and the group of children younger than 10 years. Tests for trend using polynomial orthogonal contrasts indicated a significant linear trend for change in
ACE2 expression with advancing age group (
P ≤ .05).
Discussion
The results from this study show age-dependent expression of
ACE2 in nasal epithelium, the first point of contact for SARS-CoV-2 and the human body. Covariate-adjusted models showed that the positive association between
ACE2 gene expression and age was independent of sex and asthma. Lower
ACE2 expression in children relative to adults may help explain why COVID-19 is less prevalent in children.
3 A limitation of this study is that the sample did not include individuals older than 60 years.
Few studies have examined the relationship between ACE2 in the airway and age. A study of bronchoalveolar lavage fluid from 92 patients with acute respiratory distress syndrome reported no association between ACE2 protein activity and age,
5 but epithelial gene expression was not examined, and ACE2 protein may be variably shed into bronchoalveolar lavage fluid. Furthermore, the lung and nasal environments are distinct, with known differences in gene expression.
6 This study provides novel results on
ACE2 gene expression in nasal epithelium and its relationship with age.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
Article Information
Corresponding Author: Supinda Bunyavanich, MD, MPH, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave #1498, New York, NY 10029 (
supinda@post.harvard.edu).
Accepted for Publication: May 7, 2020.
Published Online: May 20, 2020. doi:
10.1001/jama.2020.8707
Author Contributions: Dr Bunyavanich had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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