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.