Kids’ susceptibility to seasonal viruses may protect them from COVID-19

Any parent of young children can tell you kids are more susceptible to common colds than adults. But a new study suggests that susceptibility to a variety of respiratory infections may be part of what protected children from severe COVID-19.

In a new study, Yale researchers found that the presence and preponderance of respiratory viruses and bacteria in children's noses was associated with stronger nasal immune responses, which, they say, could be part of why kids were less likely to get severe COVID-19 during the pandemic.

The findings were published July 1 in the Journal of Experimental Medicine.

Throughout the COVID-19 pandemic, children have been, somewhat puzzlingly, less affected than adults. Researchers have been trying to understand why this might be. Over the last couple of years, several studies have shown that children have stronger nasal activation of their innate immune response - a broad, general anti-infection defense system - than do adults, with or without SARS-CoV-2 infection.

"The prior studies showed that there was something different about kids in terms of having better defenses at the barrier where the virus tries to penetrate the body," said Ellen Foxman, associate professor of laboratory medicine and immunobiology at Yale School of Medicine and senior author of the study. "But the unanswered question was, why do kids have better defenses?"

To better understand what drives heightened nasal immune responses in children, researchers collected over 600 nasal swabs that had been administered to children with and without respiratory symptoms in 2021 and 2o22. Those swabs had been used to test children for COVID-19 prior to elective surgeries or as part of COVID-19 screening in the emergency department. The samples were frozen at the time and recently used to examine other nasal infections and innate immune responses.

For the new study, researchers tested the swabs for 15 additional respiratory viruses and three types of bacteria that can cause respiratory illness. They also tested for proteins that indicate innate immune activation.

In samples from the summer of 2021 and from January 2022, respiratory viruses were found in about one-third of children, and bacteria in one-fourth to one-third of children. In June and July 2021, common cold viruses were found most often, whereas during the Omicron surge in January 2022, SARS-CoV-2 was the most frequent virus detected. However, many other viruses and bacteria were also detected in children's noses during both seasons. Rates were highest in the youngest children, with 90% of symptomatic children and about half of asymptomatic children under the age of five testing positive for viruses, bacteria, or both.

"We also found that heightened innate immune defenses directly correlated with the type and amount of microbes in the nose," said Foxman. "So for kids that had viruses in their noses, the antiviral defenses were heightened. And the more virus they had in their noses, the higher those antiviral defenses were."

Children with disease-causing bacteria also showed heightened antibacterial immune defenses.

Overall, the findings showed that increased nasal innate immune defenses in children were a reaction to the viruses and bacteria present, said Foxman.

To better understand if nasal defenses change over time in the same child, the researchers also swabbed the noses of 20 one-year-olds during healthy well child check-up appointments and then re-swabbed them one to two weeks later.

Of the 20 children tested, only four children had no virus detected in either sample. Many children had viruses detected in one sample but not the other.

"We could see that the change in viral load corresponded to the change in antiviral defenses in the same child across the two tests," said Timothy Watkins, a graduate student in Foxman's lab and the lead author of the study. "Our results show that children are getting mild or sometimes asymptomatic infections quite often, leading to heightened barrier defenses."

Innate immunity is the broad, non-specific defense system that protects against many different pathogens that enter the body. Adaptive immune responses, such as antibodies, are those that the body develops over time, and they protect against specific pathogens the body has been exposed to in the past.

Adults have been exposed to common seasonal respiratory viruses quite a bit over their lifetimes and have, therefore, developed antibodies against many of them that prevent specific infections. But that's not the case for children who have had fewer prior exposures. This is one of the reasons common cold viruses cause more infections in young children, leading to nasal innate immune responses being triggered more often.

"However, when SARS-CoV-2 came into our population, no one had prior exposure," said Foxman. "We hypothesize that heightened nasal innate immune responses in children due to other common childhood infections helped protect them from severe COVID. This is one of the differences between children and adults which may have contributed to reduced severity in kids during the pandemic."

Going forward, Foxman and her colleagues aim to better understand how patterns of innate immune activation in children influence responses to different types of childhood infections and vaccines.

Other authors include Alex Green, Julien Amat, Nagarjuna R. Cheemarla, Katrin Hänsel, Richard Lozano, Sarah N. Dudgeon, Gregory Germain, Marie Landry, and Wade Schulz.

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