Updated on
What did the project achieve?
“It was an immense privilege to work on this important topic in the pandemic,” says Dr Nazima Pathan of the University of Cambridge. “We hope the new insights from this unique study will ultimately lead to improved treatment for children at risk of developing severe illness from SARS-CoV-2 infection.”
During the pandemic, most children had mild or no symptoms when infected with SARS-CoV-2, the virus that causes COVID-19. However, while some children experienced severe lung problems in the same way as adults, others developed a delayed illness several weeks after infection (paediatric inflammatory syndrome (PIMS*) that made them very unwell.
To understand why some children become critically ill after SARS-CoV-2 infection, the researchers studied lung fluid and blood samples collected from 108 children – 43 with PIMS, 18 with severe COVID-19 who had been admitted into a paediatric intensive care unit, 40 with other infections unrelated to SARS-CoV-2, and seven healthy children.
“We used a range of techniques to profile the children’s immune systems in detail, including measuring gene activity and the levels of inflammatory molecules – looking for differences between the groups,” says Dr Pathan.
The team identified key differences in the immune response in children with PIMS, including changes in particular immune pathways that result in excessive activation of the immune system. They also found that their immune cells didn’t respond normally after stimulation.
“Although these findings are preliminary, they could lay the foundations for tests that can predict children who are at risk of becoming critically ill after SARS-CoV-2 infection – helping doctors to select the most effective treatments as soon as possible,” says Dr Pathan.
The team is now planning to apply their immune profiling techniques to other complex infectious diseases, such as immune-mediated diseases in children and hospital acquired infections in critically ill adults and children.
*Paediatric inflammatory multisystem syndrome (PIMS / PIMS-TS) is also known as multisystem inflammatory syndrome in children (MIS-C), or systemic inflammatory syndrome in COVID-19 (SISCoV).
This research was completed on
Children and adults respond differently to infection with SARS-CoV-2, the virus that causes COVID-19. Thankfully, most children do not experience serious symptoms, but the few who are admitted into hospital with severe disease have a much wider range of symptoms than adults – a rare condition known as Paediatric Multisystem Inflammatory Syndrome (PIMS). Dr Nazima Pathan of the University of Cambridge is aiming to improve understanding of the underlying biology behind why COVID-19 affects children and adults so differently. She hopes to uncover new clues that could lead to new ways to prevent and treat severe illness in children, reducing both the short and long-term impact of the disease on young lives.
How are children’s lives affected now?
While children can be infected with the virus SARS-CoV-2, most will have only mild symptoms or none at all. But some will develop severe COVID-19.
“A child may become critically ill and might need hospital treatment,” says Dr Pathan. “Thankfully, most will recover from their initial illness – but they could be left with lasting problems that impact on their long-term health and well-being.”
Adults with severe COVID-19 generally have breathing difficulties and lung failure, but children can experience a much wider range of symptoms including vomiting, diarrhoea, tummy pain and headache – suggesting there may be more widespread inflammation compared to adults. This widespread inflammation seen in children with severe disease is known as Paediatric Multisystem Inflammatory Syndrome (PIMS) and usually occurs several weeks after infection.
“We urgently need to gain a better understanding of how this virus affects children – including why severe disease is so uncommon and why they have a different pattern of symptoms to adults,” says Dr Pathan.
How could this research help?
“We aim to identify biological factors that can influence a child’s risk of severe COVID-19 and/or long-term complications from the illness that may affect their quality of life,” says Dr Pathan.
The researchers will collect lung, blood and faecal samples from children with moderate or severe COVID-19, monitoring their progress during and after hospital admission. They will then link data from laboratory analyses with information about how a child responds to treatment and compare the breadth of the inflammatory response in children with PIMS to that seen in children with milder symptoms.
“By combining biological and clinical data, we hope to identify risk factors that can affect disease severity and outcomes in children,” says Dr Pathan.
The team also expects to uncover new knowledge about why children with COVID-19 are more protected from the disease compared to adults – and why they have different symptoms.
“Our findings could lead to early, personalised treatment for children who are severely affected with COVID-19, giving them the best chance of a full and rapid recovery,” says Dr Pathan.
The data generated in this study is closely aligned with other national and international studies – and will provide an important resource for researchers working on current and future pandemics.
Research table
Project details
| Project Leader | Dr Nazima Pathan, PhD FRCPCH |
| Location | Department of Paediatrics, Addenbrookes Hospital, University of Cambridge |
| Project Team |
Professor Clare E Bryant, BSc BVetMed PhD
Professor Sarah A Teichmann, FMedSci FRS Professor Nigel Klein, PhD FRCPCH Professor Mark Peters, PhD FRCPCH Dr Padmanabhan Ramnarayan, FRCPCH MD Dr Graham Taylor, PhD Dr Barney Scholefield, FRCPCH PhD Professor Hugh E Montgomery, FRCP PhD |
| Other Locations |
Department of Medicine, University of Cambridge
Cellular Genetics, Wellcome Sanger Institute, Cambridge Cambridge Department of Infectious Diseases Department of Infectious Diseases and Paediatric Intensive Care Unit UCL Great Ormond Street Hospital Institute of Child Health Institute of Immunology and Immunotherapy and Institute of Inflammation and Ageing, University Hospital Birmingham, University of Birmingham and Birmingham Children’s Hospital. Department of Medicine, University College London |
| Grant Amount | £174,358 |
| Start Date | |
| End Date | |
| Duration | 24 months |
| Grant Code (GN number) | GN2903 |
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