Why do pediatric patients tend to avoid the worst coronavirus complications?

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A team of pediatric and adult physicians from The University of Texas Health Science Center (UTHealth) and Baylor College of Medicine (both TX, USA) recently published a perspectives paper in American Journal of Physiology-Lung Cellular and Molecular Physiology describing how differences in lung physiology and immune function in children may explain why they are more often spared from severe illness associated with COVID-19 compared with adults.

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“We, as physicians, have been challenged with the question of how to treat COVID-19 and we’re learning in real time,” commented Bindu Akkanti (Memorial Hermann-Texas Medical Center, USA) a study co-author. “I knew that to figure out the best way to treat adults, we needed to get a team together to get to the bottom of why children were being spared from severe illness related to the virus.

According to the paper, although children under the age of 18 make up 22% of the US population, they accounted for only approximately 1.7% of the first 149,082 US cases, while only three pediatric COVI-19 deaths were identified by the Centers for Disease Control and Prevention 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,” remarked the authors.

One reason for this may be that children tend to have less angiotensin-converting enzyme 2 (ACE2) in their lungs than adults.

“ACE2 are important for viral entry and there seems to be less of them in children, because they increase with age,” explained Matthew Harting (UTHealth), senior author of the paper.

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The authors also noted differences in the ways in which the immune system in children responds to viruses compared with adults. This includes the retention of T cells in children, which can 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,” explained Harry Karmouty-Quintana (UTHealth), a co-author of the paper.

Patients with higher levels of T cells also have higher levels of Interleukin 10 (IL-10), 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,” Karmouty-Quintana commented. “In preclinical studies in mice, IL-10 has also shown to decrease with age.”

The team are continuing to study the disparities in COVID-19 disease progression between children and adults using blood samples from patients in different stages of the disease.

Harting concluded: “moving forward, physicians and scientists need multidisciplinary collaboration to continue learning – this is just another step in the right direction to attack this virus.”

Sources: Lingappan K, Karmouty-Quintana H, Davies J et al. Understanding the age divide in COVID-19: why are children overwhelmingly spared? Am. J Physiol-Lung C doi:10.1152/ajplung.00183.2020 (2020); www.uth.edu/news/story.htm?id=b40ccaec-50c5-465c-b2d5-a911c0344614

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