Nature March 2023

ISARIC4C researchers found the link between adeno-associated virus 2 (AAV2) and acute hepatitis of unknown cause in children. This publication in Nature is the first peer-reviewed and detailed investigation of this worldwide outbreak. At the height of the outbreak in 2022, ISARIC4C researchers rapidly released early data within the UKHSA technical reports and made it available online as a medrxiv preprint.

Within months of the start of the outbreak, ISARIC4C researchers showed that co-infection with 2 viruses and a genetic variant that made some children more susceptible to severe disease were the most likely cause of this unknown outbreak in children.

ISARIC4C in collaboration with Public Health Scotland and UKHSA found that the common virus AAV2 (adeno-associated virus 2) 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. Researchers believe that AAV2 virus may have played a key role in the development of acute hepatitis in a small number of young children around the world.

The ISARIC4C team were the first in the world to identify the AAV2 connection with recent childhood hepatitis cases.

Rapid recruitment with the help of NHS staff and data sharing with public health agencies were only possible as the ISARIC4C study infrastructure with data sharing through the Outbreak Data Analysis Platform (ODAP) was already set up.

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======= More urgent questions remain, including the mechanisms underlying disease - so work is continuing at pace with the aim to answer more of these questions to understand this disease in the coming months.