Impact case studies
AAV2 and paediatric hepatitis outbreak response
In the spring of 2022, clinicians across the UK identified a sudden increase in cases of severe hepatitis in young children. The cause of their hepatitis was unclear, creating significant uncertainty around clinical management and public-health response, including how best to treat affected children and whether the outbreak might continue to expand. Some of the earliest cases were reported in Scotland.
In response, a rapid, coordinated research investigation was activated to identify the underlying cause. This led to the discovery that adeno-associated virus 2 (AAV2) was a key driver of the hepatitis in these children. Many institutions such as the CVR, UK Health Security Agency, Public Health Scotland and NHS were involved in this investigation, showing how important it is to integrate clinical, public health and research capabilities in responding rapidly to emerging health threats.
From illness to insight: exploring a journey through paediatric research
In February 2024, we hosted an event which celebrated the collaborative research and family involvement in this outbreak response.
This video gives families an insight into what they could expect from participating in research.
Read our Recommendations Report
A recommendations report was developed following a dedicated stakeholder workshop reflecting on successes and areas for improvement across the response, drawing on experience from the very earliest cases, which were first reported in Glasgow at the Queen Elizabeth University Hospital within NHS Greater Glasgow and Clyde. Key contributors to the outbreak response took part in the discussions, including clinicians, clinical research teams, CVR research leads, and representatives from Public Health Scotland, the Scottish National Blood Transfusion Service, and the ISARIC4C Joint Chief Investigator.
Research outputs
In March 2023, a peer-reviewed research article titled 'Adeno-associated virus 2 infection in children with non-A–E hepatitis' was published in Nature. This study was led by researchers at the University of Glasgow in collaboration with NHS GG&C Royal Hospital for Children, Public Health Scotland, and members of the ISARIC WHO Clinical Characterisation Protocol UK (CCP-UK).
The study found that the adeno-associated virus 2 (AAV2) was present in a range of different samples taken from children with acute unexplained hepatitis. In contrast, AAV2 was not found to be commonly present in samples taken from children in the control groups. This study provided strong evidence that AAV2 was likely a key contributor to the development of acute hepatitis in a small number of young children around the world, resolving a critical uncertainty during the outbreak.
The paper was featured internationally in an interview with senior author Professor Emma Thomson in This Week In Virology, hosted by Professor Vincent Racaniello from Columbia University.
As part of the CVR’s digital engagement platform Research Goes Viral, host Stephen Devlin explores the publication in depth with first author and clinical lead Professor Antonia Ho, bioinformatician Dr Richard Orton, and pathologist Dr Vanessa Herder. The discussion highlights how close integration between clinical care, genomics, bioinformatics, and public-health infrastructure enabled a rapid, coordinated research response to an emerging viral outbreak.
Policy contribution
This work was conducted in real time during the outbreak, enabling rapid translation of findings into public-health decision-making. The research was led by Prof Emma Thomson. Clinical recruitment and characterisation were led by Prof Toni Ho, with key contributions from Dr Richard Orton, Dr Chris Davis, Prof David Robertson, Dr Ana Da Silva Filipe, Dr Vanessa Herder and Dr Patawee Asamaphan. The findings were subsequently independently verified by Great Ormond Street Hospital and by groups in the United States, including the Centers for Disease Control (CDC).
Investigation into acute hepatitis of unknown aetiology in children in England:
Critically, the outcomes from this research were incorporated into the scientific evidence base used by the UK Government, through inclusion in the UK Health Security Agency Technical Briefings on the investigation into acute hepatitis of unknown aetiology in children in England, including: