May 6, 2022 -- The CDC is now investigating 109 cases of unexplained hepatitis cases in children in 25 states and U.S. territories, the agency said Friday. Nearly all these cases (90%) required hospitalization and 14% of children infected needed a liver transplant. While the majority of affected children have recovered, officials said, there have been five reported deaths.

On May 4, the World Health Organization reported that there are at least 228 probable cases worldwide in 20 countries.

More than half of U.S. cases have tested positive for adenovirus, but officials said they did not yet know if the virus is the cause of these cases. Other factors continue to be considered, including environmental exposures, medications, and other infections.

These children have tested negative for other more common viruses that may cause hepatitis, like Hepatitis A, B, C, D, and E, and COVID-19 vaccination is not the cause, officials stated. The median age of affected children is 2, officials said, meaning that most are too young to be eligible for the COVID-19 vaccine.

Not all these cases could therefore be linked to the current investigation, officials said.

Any links between these cases and COVID-19 itself remain unclear.

“We are not aware of any cases that are occurring in kids that have documented COVID-19,” said Jay Butler, MD, deputy director of Infectious Diseases at the CDC. A CDC analysis published April 29 found that none of the children infected in Alabama had a history of COVID-19 infection.

“We are working to be able to assess whether or not some of the kids have … evidence of past infection,” he added.

CDC ‘Casting a Wide Net’

The public health agency noted that they are using a broad definition for pediatric hepatitis cases, which includes children under 10 who have elevated liver enzyme levels.

“We’re casting a very wide net to help broaden our understanding,” Butler said. “Those are the cases that we want to do a deeper dive on.”

The CDC is investigating cases in Alabama, Arizona, California, Colorado, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Louisiana, Michigan, Minnesota, Missouri, North Carolina, North Dakota, Nebraska, New York, Ohio, Pennsylvania, Puerto Rico, Tennessee, Texas, Washington, and Wisconsin.

The agency did not specify where the deaths occurred. These cases have all occurred in the past 7 months, so some may not be recent, Butler said.

Officials noted that there has not been a significant increase in pediatric hepatitis or liver transplants in the United States compared to prior to the pandemic, but this was based on an early analysis of limited data, and this may change.

There has been an uptick in hepatitis cases in children in the United Kingdom, but case numbers in other European countries have remained “relatively small,” Butler said.

The CDC advises health care providers to continue their standard workup for children with acute hepatitis as well as consider testing for adenovirus. Parents and caregivers should be aware of the symptoms of hepatitis, which include vomiting, dark urine, light-colored stools, and jaundice.

“We know this update may be of concern, especially to parents and guardians of young children,” Butler said. “It’s important to remember that severe hepatitis in children is rare, even with the potential increase in cases that we are reporting today.”