2023-10-31 12:13:45
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A more active immune system in the respiratory tract offers protection once morest severe disease. In adults without symptoms, certain gene variants play a role.
Frankfurt – From the beginning of the corona pandemic, it was noticeable that some people show only weak symptoms or no symptoms at all when infected, while others become seriously ill or even die from it. It quickly became clear that Covid-19 is mild for most children, while older age is associated with an increasing risk for adults. Nevertheless, there have always been older people who hardly notice an infection with Sars-CoV-2, even when no vaccination was yet available. Conversely, it can also hit young, previously healthy people hard.
Children usually get little more than a cold when they are infected with corona. © imago images/Westend61
Researchers from Germany and the USA have now found what they are looking for in their search for the reasons. Scientists at the German Cancer Research Center in Heidelberg (DKFZ) found that the immune system in the upper respiratory tract – nose, paranasal sinuses, throat and larynx – is significantly more active in children than in adults and is therefore better equipped to fight the virus. According to the DKFZ, “less than 0.001 percent of infected school children died of the infection during the pandemic,” while the figure for “very elderly people” was more than ten percent.
Epithelial cells of healthy children permanently in “heightened alert”
As early as 2022, a team from the DKFZ and the Berlin Institute of Health at the Charité discovered that the epithelial cells in the nasal mucosa of healthy children are permanently on “increased alert”. This has to do with the fact that certain proteins in the nasal mucosa are more active – so-called sensor proteins, which recognize pathogens by their genetic material and initiate an interferon response. Interferons are produced primarily by white blood cells during the inflammatory reaction to infections or tumors; they are part of the innate immune response.
For the current study, the team led by virologist Marco Bilder from the DKFZ examined the cellular composition of the mucous membrane in the nasal cavities of healthy children in more detail. Main results: “Compared to adults, the nasal mucosa of children is not only populated by significantly more immune cells,” says a statement from the DKFZ: “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 the virus sensor proteins. In this way, children’s mucous membrane cells might “react much more quickly to infection with Sars-CoV-2,” explains Binder.
This means that children have an “innately strong protective mechanism once morest respiratory infections,” which is probably also effective in defending once morest other viruses. This difference became particularly clear during the pandemic because everyone’s immune system came into contact with Sars-CoV-2 for the first time. “In the case of 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 once morest the pathogens.” As a result, children’s better defenses once morest viruses are “no longer as noticeable.”
Great importance of prophylaxis for respiratory infections
In Binder’s opinion, it might be worthwhile to use these findings to research into prophylaxis for respiratory infections. “Such approaches might aim to mimic the cellular composition of children’s mucosal tissue, for example through inhalation of low-dose cytokine preparations.”
But why is it, when adults remain asymptomatic despite infection? According to an article in the specialist magazine “Jama”, this applies to one in five people. A group led by Jill Hollenbach, professor of neurology, epidemiology and biostatistics at the University of California San Francisco, thesis that there are genetic reasons for this and that existing T-cell immunity as a remnant of previous infections with corona cold viruses plays a role plays. The study was published in the journal “Nature”.
When looking for genetic reasons for different courses, the researchers focused on the human leukocyte antigens (HLA), of which there are thousands of variations. They encode proteins that are important for defending once morest pathogens. If a virus attacks a cell, HLA proteins on the surface alert suitable T cells, which kill the infected cell.
Study on Corona started early in the pandemic
For their study, which started early in the pandemic, the researchers used a list of almost 30,000 potential bone marrow donors in the USA whose human leukocyte antigens had been sequenced in detail. You were asked to record possible symptoms online if you tested positive for the coronavirus. More than 1,400 participants tested positive for Sars-CoV-2 during the course of the study, and 136 of them reported that they did not feel the infection. The evaluation showed that a certain variant of the human leukocyte antigen (HLA-B*15:01) was found in 20 percent of these “asymptomatic” people, but this only occurred in nine percent of the participants with Covid symptoms. People who had two copies of this gene variant, i.e. inherited it from both parents, were eight times more likely to develop no symptoms than those who did not have a single copy of this gene variant.
An analysis of the T cells also showed that the participants with the “protective” HLA variant already had killer T cells that were effectively directed once morest Sars-CoV-2 before the pandemic began. The researchers conclude that people with this gene variant who have previously been exposed to corona cold viruses develop an immunological memory that recognizes Sars-CoV-2 during a later infection and quickly kills infected cells. Since this one HLA variant only accounted for 20 percent of asymptomatic cases, Jill Hollenbach suspects that there are other genetic and non-genetic factors that may also play a role.
In HIV infections, variants of the human leukocyte antigens influence, among other things, how strongly the pathogens multiply and whether someone develops the clinical picture AIDS or not.
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