The investigation—involving a study of adenovirus in children who don’t have liver disease—is a potential departure from the leading theory that adenovirus, a pathogen that usually causes cold- or flu-like symptoms, is solely responsible for the outbreak.

As researchers examine the liver biopsies of affected children and fail to find adenovirus, “it does raise our suspicion that something else is going on here,” said Dr. Jay Butler, deputy director for infectious diseases at the U.S. Centers for Disease Control, on a Friday media call.

Nonetheless, adenovirus 41, a particular strain usually associated with gastrointestinal issues, plays an “important role” in the agency’s leading hypothesis, Butler said, adding that prior infection with COVID or another factor could also play in.

Since October, 180 U.S. children with acute hepatitis of unknown origin, often presenting with jaundice, have been reported in 26 states and territories, Butler said. The median age of those affected is 2. Reported cases increased by 71 in the past two weeks.

Eight percent of U.S. cases have required liver transplant, and six deaths are under investigation. More than 90% of patients were hospitalized, according to the CDC.

As of April 23, at least 160 cases had been reported in Europe, with approximately 10% requiring liver transplants and at least one death, according to the World Health Organization.

Many, if not most, recently reported U.S. cases were retrospective, meaning that they occurred some time since October but were only recently reported, Butler said, adding that there hasn’t been an onslaught of new cases reported.

While adenovirus 41, in particular, “seems to be playing a role in these kids,” questions have been raised about “cofactors that may be making infections more likely,” Butler said.

Researchers are looking at patients to see how many had past COVID infection or whether any met the criteria for MIS-C, a rare, multisystemic inflammatory disorder that has been reported in patients who have had COVID or who have been in contact with those who have, he added.

U.S. medical officials in particular have been quick to implicate adenovirus as a potential cause, as it’s been detected in nearly half of children with hepatitis of unknown cause. Other potential culprits include COVID, and hepatitis A, B, C, D, and E viruses, according to the CDC.

But adenovirus “does not fully explain the severity of the clinical picture,” according to a late April report by the World Health Organization. “Infection with adenovirus type 41, the implicated adenovirus type, has not previously been linked to such a clinical presentation,” the report stated.

Usual symptoms of adenovirus type 41 include diarrhea, vomiting, fever, and respiratory symptoms, according to the WHO, and the strain isn’t known to cause hepatitis in otherwise healthy children. Other types of adenoviruses have been associated with liver failure, but only in immunocompromised kids.

“Adenovirus is common, so the fact that it’s around a lot and the fact that we haven’t really seen the pattern before makes it important to differentiate” from other potential causes, Dr. Georges Benjamin, head of the American Public Health Association, told Fortune this week. “We should not close our search for other viruses.”

While active COVID infections were found in a smaller percentage of U.S. and U.K. patients than adenovirus, evidence of past COVID infection wasn’t reported, or perhaps even sought, in the majority of cases. 

Such testing is now underway in the U.K., according to health authorities there. Of the 173 U.S. pediatric acute hepatitis patients reported in the U.S. as of last week, 12% had an active COVID infection, and 74% of the 19 tested showed evidence of prior infection. The CDC is “in the process of obtaining” blood samples from children to test for COVID antibodies, Butler said Friday.

Other potential causes of the mysterious cases of hepatitis include a new strain of adenovirus, exposure to a toxic agent, and a new hepatitis virus, officials have suggested. It’s also possible that the world is seeing a normal pattern of hepatitis in children that has previously been under-reported. Reporting of hepatitis is not mandatory in the U.S., Butler said Friday.