What's causing the mysterious, severe hepatitis in kids? Here are 3 theories

The Centers for Disease Control and Prevention are investigating a growing number of cases of hepatitis in children with an unknown cause — and whether a previous COVID-19 infection may play a role in the illnesses.

In a statement Wednesday, the agency said the number of cases under investigation has reached 180, up from 109 on May 5. But the agency clarified that this doesn't mean that more children are getting sick. Many newly reported cases are not actually recent. The CDC is investigating cases that have been occurring since October 1, 2021.

Hepatitis is an inflammation of the liver and is typically caused by one of the hepatitis viruses. But in these cases, all the typical causes of hepatitis have been ruled out.

Cases are under investigation in 35 states and Puerto Rico. The CDC previously said it was investigating five deaths in connection to the outbreak, all occurring before February. About 9% of children in the U.S. with the illness have needed a liver transplant.

The CDC is investigating an adenovirus infection as a possible cause of the hepatitis, calling it a "strong lead" in the Wednesday statement, as nearly half of the 180 children had tested positive for it. Adenoviruses are common and typically cause cold-like or gastrointestinal symptoms. A specific type of adenovirus — adenovirus 41 — is also being investigated.

In the first cluster of cases that the CDC investigated, nine children in Alabama, all tested positive for adenovirus, with five testing positive for adenovirus 41. Adenovirus 41 is not known to cause hepatitis in otherwise healthy children, but most, if not all, of the children in the CDC investigation were previously healthy.

Is COVID behind the hepatitis in kids?

The CDC statement also revealed that it is looking into a connection to SARS-CoV-2, the virus that causes COVID-19. There's no evidence that it's the direct cause, NBC News reported, but one hypothesis is that a previous COVID-19 infection may predispose some children to "adenoviral hepatitis," Dr. Rick Malley, an infectious disease pediatrician at Boston Children's Hospital, told TODAY.

A recent report in The Lancet put forward a similar theory. As Malley, who was not involved in the research, summarized it: "The hypothesis ... with this Lancet article — and again, I think it's a hypothesis — is that somehow getting COVID changes the ability of children to respond in one way or another to other viruses."

"It stands to reason that, in the context of a new virus that has had such pandemic proportions as SARS-CoV-2, when you ... hear that something unusual might be happening in children, it would be absurd not to at least investigate the possibility of a connection," Malley added.

Still, he stressed that the investigation is in early stages, explaining, "This is hypothesis generation. It's not hypothesis testing. We're just saying, is this a possibility?"

Malley offered two other hypotheses, as well. The "most simple," he said, is that a new version of adenovirus 41 has been circulating, and it has slightly different properties or mutations that make it favor infection in the liver. Another possible theory is that these children may be more susceptible to hepatitis for whatever reason but weren't exposed for two or so years due to pandemic restrictions.

"All of a sudden, you remove all these barriers, and all these kids that would normally have ... hung out with one another for two and a half years, they’re now exposed to one another," Malley explained. "In a way you’re almost catching up the number of cases that you might have seen over the last two and a half years."

Asked why the cases seemed to start picking up in October, Malley said, "I don't think anybody has the knowledge right now to say why we're seeing it now and not before. ... We have no idea. Maybe ... this weird adenovirus 41 is causing this, and that has nothing to do with COVID-19. That's still a possibility."

He went on to stress the importance of parents knowing the signs of hepatitis and being aware of cases in their community — not because they should change their behavior but because they should be extra quick to seek medical attention if their child develops symptoms, especially a yellowing of the skin or eyes. Other signs of hepatitis include abdominal tenderness or pain, fatigue, dark urine or light stools, nausea, vomiting or abdominal swelling.

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