One of the few silver linings of the ongoing pandemic is that children, relatively speaking, have been spared the onslaught of the novel coronavirus (Sars-Cov2).

Studies of hospitals in the UK have revealed that the overall risk of death or severe disease from the viral attack is very low in children. Data collected by the Centers for Disease Control and Prevention from hospitals across the US suggest that those under 18 have accounted for less than 2 per cent of hospitalisations due to Covid-19 between March 2020 and late August 2021. A survey that tested 28,975 children (6-17 years) for antibodies against Sars-Cov2 by the Indian Council of Medical Research found that over half of them had detectable antibodies (seropositive) and didn’t suffer from severe disease.

Why are children naturally better at controlling Sars-Cov2 infections than adults? Are their immune systems more primed to fight off the virus? A team of German scientists found that a child’s immune system is indeed much more active in the upper airways than in adults, making it better armed to fight off the virus. The findings were recently published in the journal Nature Biotechnology.

The researchers from the Berlin Institute of Health at Charité (BIH) found that children’s immune systems use a special mechanism in the mucous membrane of their airway that protects them from the attack of novel viruses. The scientists, led by Irina Lehmann and Roland Eils, director of the BIH Digital Health Center, examined differences in the cell types of the mucous membranes of children and adolescents. They found that children not only have many more immune cells in their mucous membranes but also produce a type of interferons — or proteins, that are part of our natural defences — more quickly, and these are crucial for fighting viruses. As a result, these key molecules may also provide protection from the dysregulation of the immune system that occurs in many severe cases of Covid-19.

Eils spoke about this research at the Berlin Science Week, a 10-day international science festival that brings together the world’s most innovative scientific organisations every year in early November. He explained to The Telegraph in an exclusive interview, “We as adults rely very much on the ‘adaptive’ immune system, but children rely very much on their ‘innate’ immune system which is a very primitive form of immune system that exists in worms and other lower-level organisms.”

The researchers had collected samples for these investigations from the nasal mucosa of both healthy and Sars-Cov2-infected children and adults, and studied how the disease progressed. Most of the infected children had only mild symptoms like a cold or slight fever, and these subsided after a few days. In the samples obtained from the children, the BIH researchers performed single-cell transcriptome analyses — in other words, they examined which genes were transcribed or read in which cells and how frequently this occurred. The comparison of the cells obtained from children and adults provided a surprising result. The immune and epithelial cells of the nasal mucosa of healthy children were already on high alert and prepared to fight Sars-Cov2.

Explained Eils, “The innate immune response works through the activation of unique pattern recognition receptors that sense a potentially harmful pathogen — in this case the Sars-Cov2 virus — and immediately initiate primary defence triggering interferons.” These receptors are part of a “pre-activated antiviral innate immunity system” in children that can quickly recognise the viral RNA as soon as it enters the cell. In adults, this antiviral response is usually weak and slow — it can take about two days to get activated — which allows the virus to proliferate massively in the cell.

According to Eils, children’s immune systems can sense novel viruses — even if they haven’t encountered them ever — “all over the place”. “This is the reason you find little ones often coming back from pre-school with running noses, but not getting severely sick,” he said. To verify that it is indeed this mechanism that leads to the rapid elimination of Sars-Cov2 and provides protection for children, the BIH researchers collaborated with a team at the German Cancer Research Center in Heidelberg.

These researchers infected lung epithelial cells with Sars-Cov2 in the laboratory and were able to demonstrate that the presence of precisely those pattern recognition receptors that are more pronounced in children determines whether infected cells can respond quickly enough to virus infection. As observed in these lab experiments, Sars-Cov2-infected children showed a significantly stronger interferon response than adults, especially during the first days of infection. This finding is consistent with previously published studies indicating that children have a lower viral load and eliminate the virus more rapidly than adults.

Now the team led by Lehmann and Eils is thinking about how to translate the findings into clinical practice. “We learned from this study that there are apparently not only risk factors for severe Covid-19 progression, but also protective factors,” said Lehmann in a press statement. She adds, “By knowing which pre-activations are helpful in protecting against certain viruses, we could now think about specifically inducing such an antiviral response before infection occurs and thus possibly protect at-risk patients from severe disease.”