Cardiovascular impact of COVID-19 with a focus on children: A systematic review

Table 1 Hypothesized mechanism for the lower susceptibility of children to coronavirus disease-2019

Factor involved	Explanation
ACE2 receptor	The ACE2 receptor is necessary for the entry of the COVID-19 into the cells. It is postulated that in children the development, function, or activity of this protein could be lower. Also, ACE2 receptors are up-regulated in those with chronic obstructive pulmonary disease or hypertension, which may partially explain more serious disease in those with comorbid conditions.
Reduced exposures	Children may have fewer opportunities than adults to be exposed to the virus or to those with COVID-19. Children have fewer outdoor activities and make fewer international trips, making infection less likely. Compared to adults, children have had less lifetime exposure to toxins such as cigarette smoke and air pollution, factors which may affect the health of an individual’s epithelium.
Comorbidities	Compared to adults, children have a low rate of comorbidities and most children with COVID-19 infection are young and previously healthy.
Other viruses	Children are susceptible to a wide variety of viral illnesses. The presence of other viruses may limit COVID-19 infection by competitive mechanism. In addition, cross-reactive antibodies generated by exposure to other viruses may cause a partial protective response.
Inflammatory response	Children have fewer pro-inflammatory cytokines secretion than adults. This may mean that adults experience a more pronounced inflammatory response than children with a similar exposure to SARS-CoV-2.
Immune response	Children have a more active innate immune response than adults. The innate immune system, which acts earlier than the adaptive immune response, is more active in children, and may prevent more serious illness. Natural involution of the thymus over time leads to a decline in circulating naïve T cells. Due to this normal process, immune systems in adults are less able to be adaptive than those of children.

ACE2: Angiotensin-converting enzyme 2; COVID-19: Coronavirus disease-2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.