The World Health Organization said Saturday that 12 countries have reported at least 169 unusual cases of hepatitis in children, with 17 of the children having undergone liver transplants as a consequence. At least one child has died.
The WHO’s European division, which is taking the lead on the investigation into the mysterious outbreak, urged countries to look for, investigate, and report similar cases.
“Although the numbers aren’t big, the consequences have been quite severe,” Richard Pebody, who heads the high threats pathogen team at the WHO’s European division, told STAT in an interview. “It’s important that countries look.”
The affected children range in age from 1 month to 16 years, though the majority are younger than 10 and many are under the age of 5, Pebody said.
Countries that have reported cases are the United Kingdom (114), Spain (13), Israel (12), the United States (9), Denmark (6), Ireland (less than 5), the Netherlands (4), Italy (4), France (2), Norway (2), Romania (1), and Belgium (1). Pebody would not say which country had reported a death.
The numbers may already be out of date. The U.S. has seen 11 cases — nine in Alabama and two in North Carolina.
The first Alabama cases date back to October and November of 2021, the earliest known cases. Pebody said most of the others are more recent. Authorities in Scotland — whose identification of a cluster of cases marked the first published report on these cases — have reported 14 cases dating from January to mid-April.
Severe hepatitis in previously healthy children isn’t common. What makes these cases of serious liver inflammation more unusual is that they haven’t been caused by the typical culprits — the hepatitis viruses labeled A through E that are the most common causes of the condition.
Instead, suspicion has centered on an unexpected suspect — an adenovirus, specifically adenovirus type 41. At least 74 of the affected children have tested positive for adenovirus infection and molecular testing has turned up evidence of adenovirus 41 in 18 of those children.
Both the U.K. and the Netherlands have reported that they are seeing increasing adenovirus circulation, which adds to the evidence that these viruses may be playing a role.
But several issues complicate the picture.
Adenoviruses normally attack the respiratory tract, though some — including type 41 — can trigger gastroenteritis, an inflammation of the stomach and intestines that induces diarrhea. Adenovirus 41 has been linked to hepatitis in children who are immunocompromised, but hasn’t been seen to cause the condition in previously healthy children.
While many of the children were infected with adenoviruses when they developed hepatitis, 20 of them had Covid-19 and another 19 were co-infected with an adenovirus and SARS-CoV-2, the virus that causes Covid.
Authorities have ruled out any possibility that Covid vaccines might have been involved in these cases. The vast majority of the children were not vaccinated, the WHO statement said.
Pebody said a number of hypotheses are on the table. Because the illness the children have manifested doesn’t mesh with what has been previously associated with adenovirus 41, scientists are studying the virus to see if it has undergone changes that might explain the new behavior.
Another theory stems from the fact that these cases are being reported roughly two years into the Covid pandemic. Many of the affected children will have had fewer colds and other infections over the past couple of years, because of social distancing and mask wearing. That may have left them more susceptible to developing severe illness when they encountered germs. Scientists from Hong Kong reported last year that children there were ending up in hospital with rhinovirus infections — common colds — when schools reopened after months of closure.
The possibility that Covid-19 may be playing some role in this is also still on the table, Pebody said.
“At the moment, the leading hypothesis seems to be that the adenovirus seems to be possibly playing a role,” he said, though he cautioned that “these are very early days” in the investigation.