By Gary Evans, Medical Writer 

Health officials are baffled as cases of hepatitis of unknown etiology in young children are being reported globally. Some — but not all — have adenovirus type 41, which previously had not been associated with pediatric liver disease. The Centers for Disease Control and Prevention (CDC) is calling for clinicians to test for adenovirus in pediatric cases of unknown etiology. 

“Adenovirus type 41 more commonly causes severe stomach illness,” Jay Butler, MD, deputy director for infectious diseases at the CDC, said at a recent press conference. “[It commonly] occurs in immunocompromised patients and is not usually known as a cause of hepatitis in otherwise healthy children.” 

As of May 5, 2022, the CDC was investigating 109 children with hepatitis of unknown origin across 25 states and territories. More than half of them have tested positive for adenovirus. More than 90% of the U.S. cases were hospitalized, 14% had liver transplants, and five patients died, the CDC reported in a health advisory alert. 

The CDC investigation began in November 2021 when the agency was apprised that nine children in Alabama had hepatitis and adenovirus infection. None were immune compromised. Nor were any of the typical spectrum of hepatitis viruses detected, and there was no identified epidemiological link between the nine children. 

The investigation has become retrospective, looking back for similar cases that may have been missed. Symptoms of hepatitis include fever, fatigue, loss of appetite, nausea, vomiting, and abdominal pain. Adenovirus type 41 infections typically have diarrhea, vomiting, and fever, often accompanied by respiratory symptoms. 

Butler made a point of stressing that COVID-19 vaccination was not involved, and many of the children identified thus far are younger than five years of age and would not be indicated for immunization. There are also questions about whether the liver syndrome could be caused by COVID-19 infection. 

“None of the nine children in Alabama had COVID-19 infection during their hospitalization or a documented history of COVID-19,” he said. “In addition, none of them had received COVID-19 vaccine prior to being hospitalized for hepatitis. COVID-19 vaccination is not the cause of these illnesses.” 

The World Health Organization (WHO) reported at a May 10, 2022, press conference that there were 348 “probable cases” globally of the severe pediatric liver syndrome. Another 70 cases were still under investigation. These latter cases are either still ruling out common hepatitis viruses or awaiting verification of findings from national health officials, explained Phillipa Easterbrook, MD, MPH, a senior scientist with the WHO. 

“Overall, there are 20 countries that have reported probable cases and then an additional 13 where these other ongoing cases are being investigated,” she said. 

Only six countries have reported more than five cases, which includes the United States with 109 and the United Kingdom (UK) with 163. In addition to the CDC investigation, which includes international collaboration, UK scientists are doing a “comprehensive series of investigations looking at the genetics of the children, their immune response, the viruses, and [conducting] further epidemiological studies,” Easterbrook said.

Approximately 70% of the cases have tested positive for adenovirus, using primarily blood assays, she said. UK researchers are conducting a case control study comparing the prevalence of adenovirus in the liver patients compared to other hospitalized children in general. 

“That will really help hone down whether adenovirus is just an incidental infection that has been detected, or there is a causal or likely causal link,” Easterbrook said.

For more on this story, see the June issue of Hospital Infection Control & Prevention. 

Gary Evans, BA, MA, has written numerous articles on infectious disease threats to both patients and healthcare workers. These include stories on HIV, SARS, SARS-CoV-2, pandemic influenza, MERS, and Ebola. He has been honored for excellence in analytical reporting five times by the National Press Club in Washington, DC.