Study sheds new light on severe infections and inflammatory diseases in children

Around 100 children who were treated in Evelina London Children's Hospital's paediatric intensive care unit were involved in an important study that aimed to increase understanding of what happens to a child's immune system when they have a severe infection or inflammatory disease. It is hoped the study will help pave the way for better, more targeted, treatments in future.

The research, led by King's College London, Imperial College London and the University of Edinburgh, identified similarities and differences in how immune cells in the body behave when children have different infections and inflammatory diseases. The findings, published in Nature Communications, could help to improve the way the immune system is treated during infections and inflammatory diseases.

Severe infections and inflammatory diseases that cause fever (also known as febrile illnesses) can be life-threatening to children. This is partly because they can stop the immune system from functioning properly. This 'immune dysfunction' makes the body less effective at clearing infections and can send the immune system into overdrive, causing damage to the body.

Despite having different causes, severe febrile illnesses often have overlapping symptoms, and the immune dysfunction caused by these illnesses is also similar to that seen in sepsis. This can make diagnosis difficult. But understanding exactly what happens to the immune system in response to different febrile illnesses could help with diagnosis and highlight new ways to treat immune dysfunction in more targeted ways.

In the study, the team looked at the different groups of immune cells in blood samples taken from 128 children with different febrile illnesses, including multisystem inflammatory syndrome of childhood (MIS-C) associated with COVID-19 infection, severe bacterial infection, severe viral infection and Kawasaki disease (a severe inflammatory disease in children), over the course of their illness. Around 100 of the children involved in the study were being treated at Evelina London Children's Hospital, with the remainder being treated at St Mary's Hospital London, Queen Elizabeth Hospital and Lewisham Hospital.

Dr Michael Carter, co-lead author of the paper, who was an NIHR academic clinical lecturer at King's College London and chief fellow in paediatric intensive care at Evelina London Children's Hospital when the work began, said: "We are so grateful to all the families who agreed to their children taking part while they were in our paediatric intensive care unit or in one of the other hospitals involved in the study. By giving their consent to small amounts of blood being taken and studied while their child was very unwell in hospital they have enabled the research team to find out more about how immune cells behave in a child's body when they have a severe infection or inflammatory condition.

Studies like this in a real hospital setting are important because current treatments for dysfunctional immunity are poor and not tailored to individual children.  Going forwards, by looking at the immune system in much more detail, we hope we'll be able to develop therapies that can treat the immune response in a more targeted way and improve outcomes for our patients.

Professor Ming Lim, Evelina London's research lead, and consultant paediatric neurologist at the Evelina London Children's Hospital said:

Evelina London Children's Hospital was among the first hospitals in the world to report multi-system inflammatory condition in children in April 2020. But our interest hasn't stopped there. Through this and other studies, our teams have continued to contribute to increasing knowledge that will hopefully support the development of more targeted treatments for febrile illnesses in future for children around the world.

The research, which was led by the University of Edinburgh's Professor Manu Shankar-Hari and Imperial College London's Professor Michael Levin, was funded by European Union funding (DIAMONDS collaboration), the National Institute for Health and Care Research (NIHR) and the Huo Family Foundation.