Evidence continues to mount that a specific strain of adenovirus could be implicated in a wave of American children who've developed acute hepatitis of unknown origin, according to U.S. Centers for Disease Control and Prevention officials.
"The evidence is accumulating that there's a role for adenovirus, particularly adenovirus 41," Dr. Jay Butler, the CDC's deputy director for infectious diseases, said in a media briefing. "The exact role that it plays, I think, is where we're really wanting to focus the investigation."
Adenoviruses are a common form of virus that can cause everything from colds to bronchitis to pinkeye, according to the CDC.
Inside the mysterious virus
At least 650 children have been diagnosed with the mysterious and severe hepatitis infection since early April, according to the World Health Organization. The cases have been reported in 33 different countries.
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At least 38 children have required a transplant, and nine have died, according to a statement from WHO. There are also 99 cases pending classification.
The majority of the cases have been reported in European countries, with 222 probable cases reported in the United Kingdom and Northern Ireland. Cases have also been reported in North America, Argentina, the Western Pacific, Southeast Asia and the eastern Mediterranean region.
According to data, 75% of the children in Europe were under the age of 5. Of the 181 cases tested for adenovirus, 60% were positive. Of the 188 cases tested for COVID-19, 12% were positive. And of the 63 cases that had data on COVID vaccination, 84% were unvaccinated, according to CBS.
The cases have been more severe and "a higher proportion develops acute liver failure compared with previous reports of acute hepatitis of unknown aetiology in children," WHO says.
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Should parents be concerned?
The cause of the outbreak remains under investigation, and WHO classifies the global risk level as moderate.
However, researchers are still struggling to determine whether there's been a true increase in cases of pediatric hepatitis in the United States, or if public health officials have simply stumbled across an existing pattern that's been revealed due to improvements in detection.
"Thus far, we have not been able to document an actual increase in the overall number of pediatric hepatitis cases," Butler stresses.
"For example, we're looking at specific emergency department visits for pediatric hepatitis, as well as liver transplant in children nationwide," Butler adds. "Currently, these numbers are stable."
The CDC recently announced that 180 pediatric hepatitis cases had been identified in 36 states over the past seven months, up from a previous count of 71 cases two weeks earlier.
However, the CDC has stressed that many of the newly counted domestic cases are "retrospective" -- meaning they were cases that are now being counted but happened as far back as October 2021.
"Of the cases altogether, [only] 7% have been over the past two weeks," Butler notes. "The vast majority going back are much earlier in the course of the investigation. If we look at graphing out the cases by the date of onset, it's relatively flat."
There had also been no reported deaths since February until recently, according to the agency. About 9% of the cases were so severe as to require liver transplants.
Is COVID the cause?
Many of the pediatric hepatitis cases have been associated with adenovirus type 41, which commonly causes diarrhea, vomiting and fever in children, sometimes accompanied by respiratory symptoms, according to the CDC. It's not been previously identified as a cause of hepatitis in otherwise healthy children.
Genetic sequencing has shown that multiple viral strains of adenovirus type 41 have been involved in the hepatitis cases, which appears to rule out an early possibility that a single newly mutated strain of the virus could be responsible, Butler says.
CDC investigators also are keeping open the possibility that COVID infections could be contributing to the hepatitis cases, Butler adds.
Researchers are performing antibody tests to determine if some of the afflicted children had a past infection with COVID and whether any had developed a serious condition known as multisystem inflammatory syndrome as a result of their COVID infection, Butler shares.
One new study, from Case Western Reserve School of Medicine in Cleveland, has found that children previously infected with COVID were, in fact, two to three times more likely to have liver function test results outside the normal range. In fact, the test results were more than twice the upper limit for healthy children, suggesting impaired liver function.
But it's already been known that kids with COVID infections sometimes have elevations in liver function tests, Butler notes.
"One of the tricky things to sort out is how much of the elevation in liver function test is specific to SARS coronavirus to infection as opposed to severe illness," Butler says. "It's not uncommon that there would be some elevation in liver function tests and even elevations in bilirubin [a marker of liver function] among children who are severely ill in the intensive care unit."
"It's unusual because this is occurring in normal, healthy kids who don't have an underlying condition," says Dr. Tina Tan, an infectious disease doctor at Ann & Robert H. Lurie Children's Hospital of Chicago. "Nobody knows the true cause, and what makes it more scary is that these kids develop very severe hepatitis."
Tips for protecting your child
Tan recommends that parents keep a close eye on children with cold and flu symptoms, and take them to the ER if they become jaundiced.
"If they start to notice that their kids are having severe abdominal pain, or that the whites of their eyes are turning a little bit yellow or their skin color's a little bit yellow, they really need to seek immediate medical attention so that the child can be worked up for hepatitis," Tan says.
Other potential symptoms of hepatitis include vomiting, dark urine and light-colored stools, Butler adds.
