These cases are serious: around 5% of infected children worldwide have required liver transplants and 22 have died. And the cause of the outbreak has been a mystery. These children do not have the viruses that usually cause the disease.
At first, 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 increase as lockdowns ended and people began mingling more, after a period of unusually low transmission.
In an attempt to find out more, Ho, along with Emma Thomson, professor of infectious diseases at the University of Glasgow MRC’s Center for Virus Research, and colleagues have been closely studying some of the affected children. In a recent study, the team evaluated nine children in Scotland with mysterious hepatitis and compared them with 58 children who did not have the disease.
The team studied blood, liver and faecal samples taken from the children, as well as throat and nose swabs. Although they could not 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 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 years old, and most people begin to develop antibodies against it around the age of three. But it had never before been directly linked to human disease, Thomson says.
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 believe the helper virus is adenovirus,” Thomson told reporters at a virtual news conference today. It is possible that the adenovirus infection followed an AAV2 infection or that both viruses arrived at the same time, he added. “Right now we can’t tell you which of these viruses is causing the disease,” Thomson said.
But viruses are not the end of the story. In genetic testing, the team noticed that children with unexplained hepatitis were much more likely to have a gene called DRB1*0401: 89% of affected children had this gene, which is generally found in 16% of the Scottish population . The gene is known to affect the functioning of the immune system. Essentially, the proteins it encodes help immune cells decide what to destroy.
