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What did the project achieve?
During the COVID-19 pandemic, it quickly became clear that children were generally less affected by infection with SARS-CoV-2 (the virus that causes COVID-19) than adults. However, the reasons for why the illness was typically milder in children remained unclear.
“We have identified key differences between how the immune system responds to the virus between children and adults, shedding light on why age is a risk factor for severe COVID-19,” says Dr Marko Nikolić of University College London. “Clinically, our findings could be used to help identify which children and adults are at greater risk of severe illness, enabling preventative steps to be taken.”
This research investigated how the immune responses of children and adults differ following infection with SARS-CoV-2. The results were published in the prestigious scientific journal, Nature, in 2021.
The team analysed blood and samples collected from the nose lining and windpipe of children and adults with COVID-19, as well as from healthy individuals. Using advanced technologies, they looked for changes in gene activity within individual cells isolated from these samples.
“To our surprise, we identified several explanations for why children are better protected from severe COVID-19 than adults,” says Dr Nikolić. “Specifically, children have a very strong immune response in the nose, which fights off the virus straight away and stops it from spreading to other parts of the body. In adults, however, the immune response in the nose is weaker, making it easier for the virus to spread elsewhere.”
Conversely, the researchers also found that the immune response in adults is much stronger in the bloodstream compared to children.
“We believe the virus can enter the bloodstream more easily in adults because of the weaker immune response in the nose. Once the virus reaches the bloodstream, it triggers a more powerful immune response, which can lead to immune-related damage to various organs,” explains Dr Nikolić. “This illustrates the dual nature of the immune system in fighting this infection – it can have both protective and damaging effects in a person infected with SARS-CoV-2.”
In follow-up work, the collaborative team across University College London, Wellcome Sanger Institute and Imperial College London also conducted a unique study in which they deliberately infected a group of young adults with SARS-CoV-2 providing an unprecedented opportunity to study how the body responds to the virus over time. They published the results of this study in Nature in 2024.
“We are incredibly grateful for the funding provided by Action Medical Research, which was absolutely essential to progress our work on identifying why children and young adults are protected from severe COVID-19, while also allowing us to identify potential avenues for preventing and treating severe disease in adults,” says Dr Nikolić.
This research was completed on
During the COVID-19 pandemic, it quickly became apparent that children are generally less affected by the virus than adults. Dr Marko Nikolić of University College London has teamed up with Dr Kerstin Meyer at the Wellcome Sanger Institute to analyse individual cells from the nose lining or immune system of children and adults, to uncover clues that could help explain this phenomenon. The results could provide immediate benefits to help inform how to effectively treat or prevent severe illness in children and adults. In the longer term, improving the understanding of how the virus enters the body could help direct public health measures so the world can be better prepared for future pandemics.
How are children’s lives affected now?
Thankfully, most children infected with SARS-CoV-2 (the virus that causes COVID-19) will have mild symptoms or no symptoms at all. But while it is very rare, some children will develop severe disease.
“One of the biggest puzzles of the pandemic is why children are generally less affected by this virus than adults,” says Dr Nikolić. “We also don’t understand why some children are more susceptible to the disease than others.”
The virus enters the body by attaching to a specific molecule, which the research team has already shown is abundant on the surface of cells lining the nose in adults. Children may have lower amounts of this molecule, making it harder for it to infect their cells compared to older people. Their immune system may also react differently to the virus.
“Understanding why children are generally less affected by COVID-19 than adults could lead to new treatments and preventive measures that could help save lives from this disease around the world,” says Dr Nikolić.
How could this research help?
“We aim to identify biological differences that can help explain why age is a risk factor for severe disease – and why some children develop a life-threatening illness,” says Dr Nikolić.
The researchers have already collected nose and blood samples from healthy children – and they now also plan to recruit children with severe COVID-19.
“We will compare the molecular signatures of individual cells from adults and children, and between those with mild and severe disease, to gain new insights into how SARS-CoV-2 gains entry into the cell and how the immune system responds to the infection,” says Dr Nikolić.
The team will also apply sophisticated computer programmes to unpick how the immune system is triggered by the virus – and to look for any immune characteristics specific to children with mild symptoms.
We hope to uncover vital new clues that lead to new approaches to prevent or reduce severe disease – and also help inform public health measures so that we can be more prepared to deal with future pandemics.
Research table
Project details
| Project Leader | Dr Marko Nikolić |
| Location | Division of Medicine, UCL Respiratory, Rayne Institute, University College London |
| Project Team |
Dr Kerstin Meyer, PhD
Professor Sarah A Teichmann, FMedSci FRS |
| Other Locations | Department of Cellular Genetics, Wellcome Sanger Institute, Cambridge |
| Grant Amount | £199,959 |
| Start Date | |
| End Date | |
| Duration | 24 months |
| Grant Code (GN number) | GN2911 |
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