The low susceptibility of children to COVID-19 illness
Adults with severe COVID-19 suffer from deadly pneumonia and
insufficient supply of oxygen throughout the body, while children show
mild to asymptomatic COVID-19 disease with fewer death cases. A study
early in the COVID-19 pandemic showed that the percentage of infected
children with SARS-COV-2 was as low as 0.9% for 0–10 years, and 1.2%
for 10–19 years old [6]. Further
analysis of the SARS-CoV-2 infected children showed that whereas there
was a 4% incidence of children with asymptomatic cases, those with mild
illness comprised 51%, and those with moderate illness 39% of the
total cases [7]. The molecular bases
of the differences in COVID-19 pathogenesis between children and adults
have yet to be fully understood.
The expression levels of SARS-COV-2 cellular receptors and co-receptors
in the children and adults could have an impact on virus infectivity and
disease severity. Angiotensin-converting enzyme-2 (ACE2) represents the
primary SARS-COV-2 receptor for viral entry and it is co-expressed with
a cluster of the transmembrane protease TMPRSS2. The role of TMPRSS2 is
cleaving the S protein of SARS-COV-1 and SARS-COV-2 into two fragments
S1, which is essential for virus attachment, and S2, for virus fusion
into the target cells[8]. Attachment
of the receptor-binding domain of the virus spikes to the ACE2 initiates
SARS-COV entry into target cells
[9,10].
As such, lung epithelial cells represent the coronaviruses’ primary
target because of the co-expression of the ACE2 receptor with TMPRSS2
protein[11].
Children show lower ACE2 expression in the lungs than adults, which
could contribute to the observed differences in disease pathogenesis
across different age groups [12]. It
has been reported that SARS infection shows slight, non-specific, and
cold-like symptoms in children younger than 12 years old that are less
pronounced than it is in adolescents
[13]. The expression levels of the
TMPRSS2 protein is regulated by the levels of androgen and androgen
receptors[14]. It is important to
note that children younger than 12 years old have a lower level of
androgen and androgen receptors than are present in adolescents and
adult men. The age-based difference in the expression levels of ACE2 and
TMPRSS2 could play a potential role in the severity of COVID-19
pathogenesis.