Differences in lung physiology and immune function in children could be why they are more often spared from severe illness associated with COVID-19 than adults, according to pediatric and adult physicians who teamed up to investigate the disparity.
The perspectives paper was recently published in American Journal of Physiology-Lung Cellular and Molecular Physiology.
According to the paper, only about 1.7% of the first 149,082 cases in the U.S. were infants, children, and adolescents younger than 18 years old. Authors noted that children under 18 make up 22% of the U.S. population. Only three pediatric deaths were identified by the Centers for Disease Control and Prevention (CDC) as of April 2020.
"These profoundly decreased rates of symptomatic infection, hospitalization, and death are well beyond statistical significance, require further examination, and may hold the key to identifying therapeutic agents," the authors wrote.
Angiotensin-converting enzyme 2s, called ACE2, are the doors that allow SARS-CoV-2, the novel coronavirus that causes COVID-19, to enter the body's cells. Children naturally have less ACE2 in the lungs than adults.
"ACE2 are important for viral entry and there seems to be less of them in children, because they increase with age," said the senior author of the paper.
In addition to fewer ACE2 receptors, the authors note the immune system in children responds to viruses differently than that of adults, leaving less opportunity for severe illness in pediatric patients. There are several different mechanisms behind the differences, including the retention of T-cells in children, which are able to fight off or limit inflammation.
"T-cells have a viral response and also an immune modulator response. In severe cases of adult COVID-19 patients, we've seen that those T-cells are reduced, so the ability to fight the virus is also reduced. In kids, those T-cells seem to be maintained, so they are still able to prevent the virus," said a co-author of the paper.
Lung tissue in children naturally has a higher concentration of regulator T-cells. Patients with higher levels of T-cells also have higher levels of Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor, an anti-inflammatory cytokine.
"IL-10 inhibits the inflammation of other components like IL-6 that are detrimental. Adults tend to experience hyperinflammatory state, where kids do not," the co-author said. "In preclinical studies in mice, IL-10 has also shown to decrease with age."
The paper's findings were made possible through collaboration in a multidisciplinary group made up of pediatric and adult physicians and scientists in pediatric surgery, adult critical care, neonatology, and molecular biology.
"We, as physicians, have been challenged with the question of how to treat COVID-19 and we're learning in real time," said another study co-author.
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