At least 600 children in at least 34 countries have developed cases of sudden severe liver inflammation, or acute hepatitis, for which doctors have no explanation.
Here is what health officials know so far:
MANY CASES HAVE BEEN DETECTED IN THE U.S., UK
As of May 18, at least 175 children in the UK and 180 in the United States have become sick since October 2021, the majority of them younger than five years old.
By comparison, doctors usually see 20 children with acute hepatitis of unknown origin each year at the UK's three specialist pediatric hepatology units, Dr Deirdre Kelly, a pediatric liver disease specialist at the University of Birmingham, told reporters on Thursday. "This is considerably more," she said.
HOW SEVERE ARE THESE CASES?
In the United States, more than 90 per cent of affected children have been hospitalized.
Most have recovered, but at least five died, according to the U.S. Centers for Disease Control and Prevention. Worldwide, more than two dozen children have needed liver transplants.
Most cases have been reported since April. The typical signs are dark urine, light stool, vomiting, and jaundice.
THE CAUSE IS A MYSTERY
Acute hepatitis is unusual in young children. No common environmental exposures have been found, such as unsafe water or food.
Doctors think a virus is most likely to blame, but none of the children has had viruses known to cause hepatitis.
Almost half of the children have tested positive for adenovirus, a common childhood virus, including some with a type called adenovirus-41F.
Adenovirus-41 is known to cause gastrointestinal symptoms such as diarrhoea, vomiting, and fever.
It has not been previously linked to this type of severe liver injury in healthy children, said Dr Rima Fawaz, a pediatric liver disease specialist from the Yale School of Medicine.
The UK Health Security Agency has said possible explanations include an exceptionally large wave of normal adenovirus infections causing unusual complications to turn up more often, a new adenovirus variant, a new SARS-CoV-2 variant, or a previously unknown infectious agent.
Researchers have raised the possibility that some earlier infection caused the children's immune system to over-react to pathogens that are usually relatively benign.
IS THERE A COVID-19 LINK?
Disease experts have ruled out a link between the hepatitis cases and COVID vaccines, as most of the affected children were too young to receive the shots.
Most of the children did not currently have COVID-19, and prior infection with SARS-CoV-2 has not yet been determined for many cases, said Dr Jason Kindrachuk, an infectious diseases researcher at the University of Manitoba, Canada.
However, some may have had mild or asymptomatic COVID infections that went unnoticed. Lingering coronavirus particles in the gastrointestinal tract could be priming the immune system to over-react to a usually-milder adenovirus with high amounts of inflammatory proteins that ultimately damage the liver.
Other experts also theorize that due to social distancing and other measures used to curb the pandemic, younger children had less exposure to adenoviruses which would have helped them build up immunity. As a result, their immune systems may be over-reacting to infection now.
"More research would be needed to confirm either theory," Fawaz said.
DETECTION BIAS MAY CONFOUND ESTIMATES
There is also the possibility that acute hepatitis rates in young children may not be as elevated as it appears.
Paediatricians may be testing for the condition more often in children with gastrointestinal symptoms, leading to the more frequent diagnosis of cases that might have gone undetected in the past.