Young children with mysterious cases of acute liver inflammation began to attract scientific and media attention. Some would recover after a transplant, but others would die. Doctors couldn't find any evidence in the children of viruses that cause hepatitis, but they did find evidence in the children of adenoviruses, a family of cold-causing viruses. A genetic search of these patients implicates another virus that was thought to be harmless.
The U.K. researchers found high AAV2 levels in 24 of 25 children with unexplained hepatitis. A group of kids without this condition had no AAV2 or adenoviruses. Young hepatitis patients are more likely to have a genetic variant that makes their immune systems overreact to Viruses.
The two preprints that were posted on medRxiv on July 19th offer new clues to the mystery of the disease, which has caused at least 22 deaths around the world.
Outside researchers are cautious about the studies. There are a small number of cases and controls. Saul Karpen says that it may be associations and not cause.
There is a rare and unexplained case of severe hepatitis in kids. In the spring, hospitals in the United Kingdom reported a rise in cases that are not related to the usual causes. The Centers for Disease Control and Prevention said in June that 334 unexplained cases have been reported in the US.
There was a surge in the number of adenoviruses in the United Kingdom. In two papers in The New England Journal of Medicine, teams from England and Alabama reported cases of adenoviruses 41, a type that causes gastrointestinal illness, in the majority of nine U.S. and 30 U.K. cases.
The teams behind the preprints in London and Glasgow wanted to make sure there wasn't a new virus emerging. They looked for about 200 different virus families using tissue samples from the U.K. AAV2 leaped out of the air. All nine Scottish cases examined and 15 of 16 separate cases from all over the UK were found to have it. Not a single one of the 158 controls included healthy children and children with hepatitis.
AAV2 was the one that I had.
The viral family to which AAV2 belongs was first found in samples that contained adenoviruses. The AAV2 can be dormant in cells until the helpers come along and make it work.
The majority of the patients had adenoviruses. A group of 12 Scottish children had an adenoviruses infection but no hepatitis, but AAV2 never showed up. The authors of the preprints did not rule out the possibility of the disease because it wasn't higher than average in the Scottish patients.
In the United Kingdom, there has been a rise in the incidence of children's diseases. Children may have been exposed to a cocktail of viruses all at once because of the relaxed COVID-19 restrictions.
The studies found that all but two of the sick children had a specific version of the genes that help shape the body's response to pathogens. The variant is very common in northern Europeans, and it's known to be linked to some diseases.
The researchers found genetic material from AAV2 in the patients' cells, but they didn't find any copies of the virus. It's possible that AAV2 may cause an immune response that harms the organs. A leader of the London team, Judy Breuer of Great Ormond Street Hospital and the University College London Great Ormond Street Institute of Child Health, said that the theory is supported by the link with HLA type.
Eric Kremer of the Institute ofMolecular Genetics of Montpellier says that a pathogenic role for AAV2 goes against everything we know. He points out that the guilt could be supported by looking at the type of antibodies to AAV2 in the children. Thomson says those studies are in the works.
The UK Health Security Agency expects to release its own study of adenoviruses in these cases this week.
Many groups are attempting to deliver therapeutic genes with AAVs, but the studies raise questions about that. Although the viruses are modified so they can't replicate, they can cause inflammation in the body, which can lead to death. According to Mark Kay, the field may want to look into the possibility of predicting whether an AAV gene therapy patient will experienceLiver toxicity.