SARS-CoV-2: A more active immune system in the respiratory tract protects children from severe disease

19.10.2023 15:00

Why is it that children and adolescents are much less likely to develop severe illnesses when infected with SARS-CoV-2 than adults? Scientists at the German Cancer Research Center have now found out: The immune system in the upper respiratory tract is significantly more active in children even before the infection than in adults and is therefore better equipped to fight the virus.

Many risk factors for a severe infection with SARS-CoV-2 are known, including high blood pressure, diabetes, obesity or previous heart disease. But the clearest and most noticeable risk factor for a severe course is age. During the pandemic, less than 0.001 percent of infected school children died from the infection. With age, the mortality rate increased almost exponentially, reaching over 10 percent in the very elderly. Children and adolescents have fewer symptoms and a shorter duration of illness than adults and especially older people, although the initial viral load is not significantly different.

Epithelial cells of the nasal mucosa of healthy children are permanently in “heightened alert”

Researchers from the BIH* in Berlin and the DKFZ took an important step towards understanding the causes of this remarkable resistance of children to severe Covid-19 disease as early as 2022: They found that the epithelial cells of the nasal mucosa of healthy children are permanently in “elevated Be on alert”. The molecular background: The sensor proteins that recognize the virus by its RNA genetic material and initiate an interferon response are significantly more pronounced in the cells of the children's nasal mucosa than in adults. This means that the virus can be quickly recognized and combated as soon as it arrives in the cell.

But why is it that children's nasal mucosa is so much better prepared to defend itself against SARS-CoV-2? To clarify this question, Marco Binder and his team at the DKFZ, together with their colleagues from Berlin, examined the cellular composition of the mucous membrane in the nasal cavities of healthy children in more detail at the level of individual cells.

Children's nasal mucosa is populated by significantly more immune cells

The main result of the DKFZ virologists: Compared to adults, children's nasal mucosa is not only colonized by significantly more immune cells. Even in healthy, uninfected children, the individual immune cells also produce more inflammatory messenger substances, so-called cytokines. The immune system communicates with the mucous membrane cells via these messenger substances and stimulates them to produce sensor proteins.

“We were able to show that the presence of low doses of these cytokines keeps the airway epithelial cells on heightened alert. The mucosal cells then prepare themselves by increasing the production of virus sensor proteins and can thus react much more quickly to the infection with SARS-CoV-2.

This means that children apparently have an innately strong protective mechanism against respiratory infections, which is probably also effective in defending against other viruses. “During the pandemic, this difference was particularly clear because everyone’s immune system came into contact with this coronavirus for the very first time,” explains Marco Binder. “With other infections such as a cold or flu, adults have already built up an immune memory through repeated contact with the viruses, which helps to defend themselves against the pathogens. As a result, the effectiveness of the children's better virus defenses is no longer as clearly noticeable."

And the DKFZ virologist mentions another special feature: “SARS-CoV-2 reproduces extremely quickly in our cells and also has many tricks up its sleeve to switch off the sensors of the cellular virus alarm system. Therefore, the child's protective mechanism is particularly important with this pathogen. With other respiratory infections, the difference between children and adults may not be so dramatic.” The scientist would like to investigate this question further in future research projects.

Marco Binder assumes that it could be worthwhile to research prophylactic strategies for SARS-CoV-2 and other respiratory infections. “Such approaches could aim to mimic the cellular composition of children’s mucosal tissue, e.g. B. through inhalation of low-dose cytokine preparations.”

Original publication

Vladimir G. Magalhaes, Soren Lukassen, Maike Drechsler, Jennifer Loske, Sandy S. Burkart, Sandra Wust, Eva-Maria Jacobsen, Jobst Rohmel, Marcus A. Mall, Klaus-Michael Debatin, Roland Eils, Stella Autenrieth1, Aleš Janda, Irina Lehmann, Marco Binder: Immune–Epithelial Cell Cross-Talk Enhances Antiviral Responsiveness to SARS CoV-2 in Children
EMBO Reports 2023, DOI: 10.15252/embr.202357912

* BIH: Berlin Institute of Health at the Charité