PURPOSE:

• Coronavirus disease 2019 (COVID-19) is an infection caused by the SARS-CoV-2 virus
• The virus is known to target the angiotensin converting enzyme 2 (ACE2) co-receptor
• Approximately <2% of COVID-19 cases are found in younger children
• Bunyavanich et al. (JAMA, 2020) studied the ACE2 gene in nasal epithelium to determine if differing expression based on age may explain the distinct difference in infection rates between children and adults

METHODS:

• Retrospective examination of nasal epithelium
• Sample sources
  • Collected from individuals aged 4 to 60 years (2015-2018)
  • Initial collection was performed for a study on nasal biomarkers of asthma
• Specimen collection at time of initial study
  • Cytology brush used to collect samples | Specimens stored and then RNA extracted within 6 months | Batch sequenced in 2018
• For the present study
  • ACE2 gene expression was measured (amount of RNA indicates quantitative expression of a gene)
  • Adjustments made for co-variates (sex and asthma)
  • Age categories: <10 years | 10 to 17 years | 18 to 24 years | Adults (≥25 years)

RESULTS:

• 305 individuals included
  • Ages: 4 to 60 years
  • Balanced between males and females
  • 49.8% had asthma (due to aim of the original study)
• ACE2 gene expression was dependent on age | Lowest in younger children and increased with age (measured in mean log2 counts per million; P value calculated vs <10 year group)
  • <10 years (n=45): 2.40 (95% CI, 2.07 to 2.72)
  • 10 to 17 years (n=185): 2.77 (95% CI, 2.64 to 2.90; P=.01)
  • 18 to 24 years (n=46): 3.02 (95% CI, 2.78 to 3.26; P<.001)
  • Adults (n=29): 3.09 (95% CI, 2.83 to 3.35; P≤.05)
• Tests for trend: Significant linear trend for change in ACE2 expression with advancing age group (P ≤ .05)
• The above findings were independent of sex and asthma

CONCLUSION:

• This study demonstrates that ACE2 gene expression in nasal epithelium is significantly lower in younger children and this finding trends to adulthood
• The authors point out that nasal epithelium is “the first point of contact for SARS-CoV-2 and the human body” and that “Lower ACE2 expression in children relative to adults may help explain why COVID-19 is less prevalent in children”

Learn More – Primary Sources:

Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults

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