Children's Upper Airways Primed to Combat SARS-CoV-2 Infection

Megan Brooks

August 26, 2021

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Epithelial and immune cells of the upper airways of children are pre-activated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.

The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.

The study was published online August 18 in Nature Biotechnology.

Primed for Action

Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.

A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.

"We wanted to understand why viral defense appears to work so much better in children than in adults," Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release

Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.

This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.

Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.

"Clear Evidence"

The study provides "clear evidence" that upper airway immune cells of children are "primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults," the investigators say.

Primed virus sensing and a pre-activated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.

Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus quicker than adults, consistent with the concept that they shut down viral replication earlier, the study team says.

Weighing in on the findings for Medscape Medical News, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this "interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults."

"We know there are differences in innate immunity over a lifespan but exactly how these differences might relate to viral infection remains unclear," said Wherry, who was not involved in the study.

"Children, of course, often have more respiratory infections than adults (but) whether this is due to exposure (ie, daycare, schools, etc) or susceptibility (lack of accumulated adaptive immunity over a greater number of years of exposure) is unclear," Wherry noted.

"These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and (perhaps partially) explain why children typically have milder COVID-19 disease," he added.

The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Lehmann and Wherry have reported no relevant financial relationships.

Nat Biotechnol. Published online August 18, 2021. Full text

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