Since April 2022 more than 1000 cases of children with acute hepatitis have been recorded in 35 countries. In the UK alone 268 cases have been recorded with the majority affecting children aged five or under. Of these, 40 percent required treatment in intensive care, and 12 needed a liver transplant.
Two separate studies from University College London (UCL) and the University of Glasgow, which have not yet been peer-reviewed, found no evidence linking the hepatitis cases to SARS-CoV-2 infections, the virus that causes COVID, and instead found a link with adeno-associated virus 2 (AAV2).
'While we still have some unanswered questions about exactly what led to this spike in acute hepatitis, we hope these results can reassure parents concerned about COVID-19 as neither team has found any direct link with SARS-CoV-2 infection. Our data do, however, point to AAV2 in the liver and, or blood of cases as the strongest biomarker for the hepatitis' said Professor Judith Breuer from the UCL Great Ormond Street Institute of Child Health.
The two studies, found high levels of AAV2 in liver samples from 24 of 25 patients, while the virus was only rarely present in children without acute hepatitis.
AAV2 is not typically known to cause disease and is often found in conjunction with adenoviruses that cause the common cold. Many people are infected by the age of 10, but the virus can lay dormant in cells since it cannot replicate without a 'helper-virus' such as adenovirus or herpes virus. AAV2 requires a protein from these other viruses to replicate.
One hypothesis for why the spike of cases has occurred is because transmission of adenoviruses and possibly AAV was suppressed during the COVID-19 pandemic, so an unusual number of children have been infected in a short period of time following the end of COVID control measures, which also prevented other pathogens spreading.
The Glasgow study also found that the majority of patients had an altered version of the HLA gene involved in immune responses to pathogens and also associated with some immune disorders. This variant is reasonably common in northern Europeans with 16 percent of Scottish people carrying it, but eight out of nine of the children with hepatitis in the Glasgow study had it.
Some researchers not involved in the study also cautioned that more evidence is needed. Saul Karpen from Emory University School of Medicine in Atlanta, Georgia, told Science: 'It's intriguing for sure, but it's a very small number of cases and controls. It could be associations and not causation.'