Dear Editor,
It is interesting to note that type 2 alveolar epithelial cells (AECII)
which are primarily responsible for injury repair, regeneration and
homeostatic maintenance probably have a important role in defining the
severity of coronavirus disease 2019 (COVID‐19) in children (1). The
novel virus that causes severe acute respiratory syndrome coronavirus 2
(Sars-CoV-2) uses angiotensin-converting enzyme-2 (ACE2) as its cellular
receptor facilitating virus entry and replication. As suggested in this
commentary (1), injury and depletion of AECII which express ACE2
receptor may be directly related to severity and mortality due to
COVID-19.
Children of all ages were sensitive to COVID-19 (2). It is still a
mystery why most of the children’s COVID-19 cases were milder in
clinical presentation (3, 4). It has been earlier speculated that
children were less sensitive to COVID-19 because the maturity and
binding ability of ACE2 in children may be lower than in adults.
Probably the answer lies in ACE2 gene expression. Studies investigating
factors affecting ACE2 gene expression have revealed that its
upregulation is associated with smoking, overweight, diabetes and
hypertension, all associated with increased severity of COVID-19.
Patients with severe and uncontrolled asthma have also been classified
to be at increased risk of developing more severe COVID-19 according to
Centre for Disease Control and Prevention. However, studies show that
ACE2 is involved in protective mechanisms of the lung. It may protect
against severe lung injury induced by respiratory virus infection in an
experimental mouse model and in pediatric patients. ACE2 also protects
against severe acute lung injury that can be triggered by sepsis, acid
aspiration, SARS, and lethal avian influenza A H5N1 virus infection.
Results from an American study indicate that children with asthma and
allergies have reduced ACE2 gene expression due to down-regulation of
the ACE2 receptor (5). In this cohort study, ACE2 expression in
respiratory cells was lowest in those with both high levels of allergic
sensitization and asthma (5). This might explain why children with
asthma and allergic sensitization have apparently less serious illness.
However, further investigations on factors beyond ACE2 expression are
necessary to provide insights into COVID-19 disease pathogenesis. At
present, reduced ACE2 expression appears to be a potential ”protective”
mechanism of reduced covid-19 severity in patients with asthma and
respiratory allergy.
CHANDRA SEKHAR DEVULAPALLI M.D., Ph.D.
Senior Medical Consultant and Pediatrician
Norwegian Labour and Welfare Administration (NAV), Advisory Medical
Service, work and benefits Kristiania, Oslo, Norway.
chandev@gmail.com
Conflicts of interest: None.
Finance: None.