These cases are serious: about 5% of children infected worldwide have required a liver transplant and 22 have died. And the cause of the outbreak was a mystery. These children do not have the viruses that usually cause the disease.
In the beginning, 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 be on the rise as lockdowns ended and people began to mingle, after a period of unusually low transmission.
In an effort to learn more, Ho, along with Emma Thomson, a professor of infectious diseases at the MRC-University of Glasgow Center for Virus Research, and their colleagues carefully studied some of the affected children. In a recent studythe team assessed nine children in Scotland with the mysterious hepatitis, and compared them to 58 children who did not have the condition.
The team studied blood, liver and fecal samples from the children, as well as throat and nasal swabs. Although they couldn’t find the viruses that commonly 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 age of 10, and most people start developing antibodies for it around age three. But it’s never been directly linked to human disease before, Thomson says.
The virus is unusual in that it relies on other viruses to replicate itself and make copies. “In this case, we think the helper virus is the adenovirus,” Thomson told reporters today at a virtual press conference. It’s possible that the adenovirus infection followed an AAV2 infection, or that both viruses struck at the same time, she added. “We can’t tell you at this time which of these viruses causes the condition,” Thomson said.
But the viruses are not the end of the story. In genetic testing, the team noted that the children with unexplained hepatitis were much more likely to have the DRB1*0401 gene. 89% of affected children had this gene, which generally affects 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.