Why are children less susceptible to COVID-19?

The reasons underlying the robust immunity observed in children remain unclear. According to the review paper recently published in Clinical Immunology by Kloc, there are three possible explanations. First, the child’s immune system may be trained by exposure to maternal respiratory inflammations to develop an enduring immunologic memory against respiratory viruses. Second, children may develop immunity against COVID-19 by repeated exposure in daycare facilities and schools. Third, children express reduced amounts of ACE2 (angiotensin-converting enzyme 2), a receptor for SARS-CoV-2. The expression of the ACE2 receptor is age-related and increases as the child grows older. ACE2 receptors are expressed in several tissues, including lung epithelial cells and alveolar macrophages, but those in the nasal epithelium are the mode of entry of this virus. Interestingly, ACE2 receptors expressed in the lung alveolar macrophages create hypercytokinemia, or the so-called cytokine storm, that underlies many severe and fatal COVID-19 cases.

Children initially receive immunity from their mother prenatally through placental transmission via several mechanisms. During antenatal gas, nutrient, and waste exchanges, the placenta deflects the pathogens present in the mother’s blood. The placenta also secretes several protective, anti-viral compounds including type III interferons, unique miRNAs (microRNAs), and trophomiR (miRNAs expressed by trophoblasts) that provide nutrients to the fetus while also preventing maternal rejection.

From the 16th week of gestation until birth, the fetus receives passive immunity from the mother. During this time, the placental surface cells express receptors for Immunoglobin G (IgG) that bind and pass maternal IgG antibodies to the fetus. Interestingly, IgG antibody levels in the fetus are exceptionally high and exceed even that of the mother at the time of birth. These antibodies play a critical role in protecting the newly born baby during the first few months when its immune system is underdeveloped.

The gut, with its trillions of beneficial microbiota, begins building a baby’s immune defenses at birth. Recent studies demonstrate that vaginal delivery establishes the child’s intestinal microbiota through contact with the mother’s gut microbiota.

Breast milk contains myriad factors crucial for immune development, including antibacterial compounds, chemokines, cytokines, immunoglobins, lymphocytes, neutrophils, and macrophages. There are about 5 million leukocytes in a single mL of colostrum milk. Once inside the baby, the immune cells also directly destroy pathogens they encounter. Childhood exposure to environmental pathogens trains nascent immune system to recognize and protect against future infections. The adaptive immune system is key to surviving the COVID-19 infection. There appears to be some conflicting data in the field regarding childhood immunity toward the coronavirus. Analysis of some COVID-19 clinical studies show that children are rarely infected and demonstrate less severe symptoms. Other studies suggest otherwise. Clinical data collected between January 16 and February 8, 2020 of 2,135 children aged 2-13 in China revealed nonexistent or milder symptoms compared to adults. This study also showed that the susceptibility of older children to COVID-19 infection was comparable to adults whereas infants were far more vulnerable. Taken together, these data suggest that older children are as likely as adults to get infected; however, they show less severe or no symptoms.

The rate of infection seems to be lower in children. A study in China revealed that the percentage of children infected was 0.9% in the 0-9 age group and 1.2% in the 10-19 age group. Similar results were reported in a study from Italy. According to the Italian study, the percentage of children infected was 0.5% in the 0-9 age group and 0.7% in the 10-19 age group.