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Why are severe cases in children so rare?


Irina Lehmann from the Berlin Institute of Health (BIH), together with colleagues from the DKFZ, has conducted a sensational study to find out why the child's immune system is better able to keep the Sars-CoV-2 virus in check than that of adults. 

Professor Lehmann, children seem to cope better with the coronavirus: they rarely have a severe course and often COVID-19 only manifests itself as a cold. In a new study that has caused quite a stir, you have now discovered the reason why children are better able to control the infection. What's different in children?

The explanation lies in the cells in the nasopharynx. For our study, we looked at a total of almost 270,000 cells from 42 children and 44 adults. Using single-cell analyses, we were able to observe which genes in the cells are read particularly frequently and which genes are read particularly rarely. This showed that in children the cells in the nasopharynx were already in a significantly heightened state of alert against viral invaders. Among other things, the activity of so-called pattern recognition receptors is significantly higher in children than in adults.

What do these pattern recognition receptors do?

They recognize the viral genetic material, i.e. in the case of Sars-CoV-2 the viral RNA, and then initiate a rapid immune response. In particular, they ramp up the production of interferons, messenger substances that trigger a strong immune response in infected cells.

"In children, the disease often lasts a shorter time than in adults."

Irina Lehmann is Professor of Epigenetics and Lung Research at the Berlin Institute of Health (BIH) at Charité Universitätsmedizin - Berlin. Previously, she worked for 18 years at the Helmholtz Centre for Environmental Research in Leipzig in various leading positions. (Credit: BIH/ David Ausserhofer)

And the virus has problems with that?

Yes, SARS-CoV-2 is even particularly susceptible to interferons. This virus has developed certain defense mechanisms to initially keep the interferon response low in an infected cell. In a sense, the cell is taken by surprise before it can properly defend itself and call for help. Unfortunately, this works quite well in adults. In children, however, so many pattern recognition receptors are already present from the start and the interferon response is also already switched on that the suppression mechanisms of SARS-CoV-2 largely come to nothing here. Our colleagues at the German Cancer Research Center (DKFZ), with whom we collaborated for the study, were able to show in laboratory experiments that the presence of precisely these pattern recognition receptors determines how strongly the virus can replicate in a cell.

In this way, children usually have a mild course?

Exactly, and this is matched by the observation that the disease often lasts for a shorter time in children than in adults. Especially the initial phase of a SARS-CoV-2 infection is extremely important for the further course. SARS-CoV-2 is an extremely rapidly multiplying virus. If the immune system cannot be activated quickly enough and resist, many cells will be infected very quickly. Unfortunately, this can lead to an excessive immune response: the immune system loses control, more and more immune cells are attracted and increase the inflammation in the respiratory tract with severe consequences up to lung failure. This excessive immune response is the actual cause of the severe courses of the disease. In children, the likelihood of this happening is very low, because their immune system is already alert when they come into contact with the virus.

Why then are the cells in the nasopharynx so alarmed in children, why do they show more pattern recognition receptors than in adults?

We suspect that the intensive contact between children, for example in daycare centers and schools, plays a role here. When children are in an environment where viruses are frequently in the air, their immune system is in a constant training mode - and is accordingly on the alert.

And adults are no longer in this training mode?

No, at least that's how it seems when you look at the number of immune cells in the upper respiratory tract and the activity of the genes responsible for the pattern recognition receptors. Here we see that from around the age of 20, both drop off and then remain constantly low throughout adulthood.

<p> "Personally, I think it's impressive how incredibly fast and intense the research on this pandemic and SARS-CoV-2 has been around the world."</p><p></p>

Can your findings also be helpful in protecting adults?

Ever since we saw the first results on the computer screens together with colleagues from the German Cancer Research Center (DKFZ), it was clear to us: We can learn from children how to protect themselves against the virus. If we could generate the immune response already present in children in a controlled manner in adults, this would provide increased protection against the virus. We are already thinking about how this could be done.

What could such protection look like in practice?

For example, one could imagine a nasal spray containing substances that specifically stimulate the immune system in the nose. In the morning, before you leave the house, you would take a shot and be protected throughout the day. This is still pie in the sky, but research will certainly move in this direction.

Is such a nasal spray too late for the current pandemic?

That depends on how long the pandemic lasts. The development of such a product would have to be driven forward at breakneck speed, and then there's the long road to approval and clinical trials. Personally, I find it impressive how incredibly quickly and intensively research into this pandemic and SARS-CoV-2 has been advanced worldwide.

So the pandemic has given science another kind of boost?

No, you can't put it that way. But innovative technologies of molecular analysis as well as the possibilities of data analysis, make it possible to react very quickly to challenges like the current pandemic. The ever-advancing national and international networking is also enormously important and essential for achieving scientific progress very quickly.

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