Since January, hospitals have seen unusually high numbers of previously healthy child patients with acute hepatitis (severe and with fast onset liver damage). The cases were first reported in the UK, before spreading around Europe, the US, Japan, and around the world.
In April, a likely culprit emerged: adenovirus F type 41. Adenoviruses have been found in at least 74 cases according to the World Health Organization (WHO), with 18 identified as adenovirus F type 41 – a type that hasn't been associated with liver damage previously. In the UK, where most cases have been reported, adenovirus has been found in 75 percent of those children tested. Sixteen percent also tested positive for COVID-19, though the UK Health Security Agency stressed that COVID-19 was prevalent during the time of admission, so this was not unexpected.
However, as Professor Will Irving of the University of Nottingham explained in April, this still leaves the puzzle as to why the adenovirus could be causing liver damage when it hadn't done previously.
"The link with adenovirus infection remains tantalising – a definite possibility but not yet proven," Irving said.
"There are very few case reports in the global literature of adenovirus infection being associated with hepatitis in immunocompetent children (or adults) – so if it transpires that adenoviral infection is involved in causing this disease outbreak, there will be a need to explain why the natural history of adenovirus infection has changed so dramatically in 2022."
The new correspondence piece published in The Lancet suggests a possible answer: previous COVID-19 infection, lurking in the intestines. "SARS-CoV-2 viral persistence in the gastrointestinal tract can lead to repeated release of viral proteins across the intestinal epithelium, giving rise to immune activation," the team wrote.
They explain that when the immune system is also met with adenovirus infection, this could trigger an over-reaction to the infection, releasing large amounts of inflammatory proteins and inflaming the liver.
"We hypothesise that the recently reported cases of severe acute hepatitis in children could be a consequence of adenovirus infection with intestinal trophism in children previously infected by SARS-CoV-2 and carrying viral reservoirs," they posit.
"We suggest that children with acute hepatitis be investigated for SARS-CoV-2 persistence in stool, T-cell receptor skewing, and IFN-γ upregulation, because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitised host."