Researchers at the German Cancer Research Center have found that children's upper respiratory tract immune systems respond more proactively to SARS-CoV-2 infection than adults. The reason for this difference is that the nasal mucosa of healthy children is always in a state of "high alert", with a higher density of immune cells and more secretion of pro-inflammatory cytokines. This heightened defense mechanism in children may be a natural protective response to respiratory infections.
Why do children and adolescents develop severe SARS-CoV-2 infections much less frequently than adults? Scientists at the German Cancer Research Center have now discovered that before infection, the immune system in the upper respiratory tract of children is more alert and active than that of adults and is therefore better able to fight off the virus.
There are many risk factors for a severe course of SARS-CoV-2 infection, including high blood pressure, diabetes, obesity, or pre-existing heart disease. But the most obvious and prominent risk factor for a severe course of the disease is age.
During the COVID-19 pandemic, less than 0.001% of infected school-age children died from the infection. As age increases, the mortality rate increases almost exponentially, with the mortality rate among the elderly exceeding 10%. Although there was no significant difference in initial viral load, children and adolescents had fewer symptoms and a shorter duration of illness than adults, especially the elderly.
Active defense ability of children's nasal mucosa
Back in 2022, researchers from the Berlin Institute of Health (BIH) at Charité Hospital in Berlin and the German Cancer Research Center (DKFZ) took an important step towards understanding the reasons for children's remarkable resistance to severe COVID-19 disease: They found that the nasal mucosal epithelial cells of healthy children are in a chronically "high alert" state. Molecular background: The sensor proteins that recognize viruses through the RNA genome and initiate interferon responses are much more abundant in children's nasal mucosal cells than in adults. Therefore, once the virus enters the cell, it can be quickly recognized and fought.
But why are children’s nasal mucosa better able to protect against SARS-CoV-2? To answer this question, Marco Binder and his research group at the DKFZ, together with colleagues from the BIH, conducted a more detailed single-cell study of the cellular composition of the nasal mucosa of healthy children.
The main research results of DKFZ virologists: Compared with adults, the number of immune cells in the nasal mucosa of children is significantly increased. Even in healthy, uninfected children, individual immune cells produce greater amounts of pro-inflammatory cytokines. The immune system communicates with mucosal cells through these messengers, stimulating them to produce sensor proteins.
"Studies have demonstrated that the presence of low doses of these cytokines puts airway epithelial cells into a state of high alert. The mucosal cells then arm themselves by increasing the production of viral sensing proteins, allowing them to respond more quickly to SARS-CoV-2 infection."
child protection mechanism
Therefore, children appear to be born with a strong protective mechanism against respiratory infections, which is likely to protect against other viruses as well. Marco-Binder explains: "During a pandemic, however, this difference is particularly pronounced because everyone's immune system is exposed to the coronavirus for the first time. As with other infections such as the common cold or flu, adults have already built up an immune memory through repeated exposure to the virus that helps protect against the pathogen. Therefore, the effect of children's stronger viral defenses is no longer evident."
Binder also mentioned another peculiarity: "SARS-CoV-2 reproduces extremely quickly in our cells, and it also has many tricks to turn off the sensors of the cell's viral alarm system. Therefore, infant protection mechanisms are particularly important against this pathogen. For other respiratory infections, the difference between children and adults may not be that big." The scientist plans to investigate this issue further in future research projects. "
Marko-Binder believes it may be worth exploring preventive strategies against SARS-CoV-2 and other respiratory infections. "This approach could mimic the cellular composition of children's mucosal tissues, for example, by inhaling low-dose cytokine preparations."