These cases are severe—around 5% of the children infected worldwide have needed liver transplants, and 22 have died. And the cause of the outbreak has been something of a mystery. These children don’t have the viruses that usually cause the disease.
Early on, the most obvious suspects were SARS-CoV-2, the virus behind covid-19, and adenovirus, a common virus that often causes cold- and flu-like symptoms. Adenoviruses appeared to surge as lockdowns ended and people began to mingle more, following a period of unusually low transmission.
In an attempt to find out more, Ho, along with Emma Thomson, a professor in infectious diseases at the MRC–University of Glasgow Centre for Virus Research, and their colleagues, have been carefully studying some of the affected children. In a recent study, the team assessed nine children in Scotland with the mystery hepatitis, and compared them with 58 children who did not have the condition.
The team studied blood, liver, and fecal samples taken from the children, as well as throat and nose swabs. While they were unable to find the viruses that usually cause hepatitis, they did find adenovirus in samples from six of the nine children.
The team also found another virus called adeno-associated virus, or AAV-2. This virus was found in samples from all nine children who had the unexplained hepatitis—but was not found in any of the children who did not.
This virus is known to infect most people by the time they are 10, and most people start developing antibodies for it around the age of three. But it has never before been directly linked to human disease, says Thomson.
The virus is unusual in that it relies on other viruses to be able to replicate and make copies of itself. “In this case we think the helper virus is the adenovirus,” Thomson told journalists at a virtual press briefing today. It’s possible that the adenovirus infection followed an AAV2 infection, or that both viruses hit at the same time, she added. “We can’t tell you at the moment which of these viruses is causing the condition,” Thomson said.
But the viruses aren’t the end of the story. In genetic tests, the team noticed that the children with unexplained hepatitis were much more likely to have a gene called DRB1*0401—89% of the affected children had this gene, which is generally found in 16% of the Scottish population. The gene is known to affect the way the immune system works. Essentially, the proteins it codes for help immune cells decide what to destroy.