Pediatric Hepatitis Cases May Be Linked to Adenovirus, No Connection to COVID-19 Vaccination

The CDC issued an alert on April 21 so doctors would be on the lookout for hepatitis in children. Physicians at the University of Alabama at Birmingham said in a press briefing on April 25 that they had not identified any more cases since they issued a statewide alert in February. They added that parents do not need to panic, as these cases are very rare, but people should seek medical attention if a child shows signs of liver disease, such as the yellowing of the skin or eyes, along with the more common symptoms such as diarrhea, vomiting, fever, or coughing and sneezing.

A CDC spokesperson told us that the agency has received additional reports from providers as a result of the nationwide health advisory and was working to determine if any met the current case definition. 

Other states, meanwhile, have reported their own potential cases, including Wisconsin, Illinois and North Carolina.

Worldwide, the largest outbreak has been in the U.K., which identified 145 cases this year, through April 29, “predominantly” in children under the age of 5. As in the U.S., children in the U.K. aren’t eligible for COVID-19 vaccination until they turn 5.

The U.K. Health Security Agency wrote in an April 25 update, “There is no link to the coronavirus (COVID-19) vaccine. None of the currently confirmed cases in under 10 year olds in the UK is known to have been vaccinated.”

As of April 21, the WHO reported at least 169 hepatitis cases in children 16 years of age and younger in 11 European countries and the U.S. Adenovirus was detected in “at least 74 cases,” the WHO report said, and “of the number of cases with information on molecular testing, 18 have been identified as F type 41.” In those that were tested, 20 children were positive for SARS-CoV-2 and 19 children were coinfected with SARS-CoV-2 and adenovirus.

The WHO has said there is no evidence that COVID-19 vaccination is related in any way to the hepatitis. “Hypotheses related to side effects from the COVID-19 vaccines are currently not supported as the vast majority of affected children did not receive COVID-19 vaccination,” the agency said in its April 23 disease outbreak report.

In an April 28 live Q&A, WHO officials repeated that there is nothing to support a link to the COVID-19 vaccines, as most of the children with hepatitis haven’t been vaccinated, nor are they eligible to be vaccinated yet, because of their age.

Since so many of the children have tested positive for an adenovirus, many investigators consider the virus a top contender to explain the hepatitis. But even if that’s the case, it’s likely there are other factors involved. Experts remain open to other possibilities as well, as the cause is still very much an open question.

“The leading hypothesis at present is that the hepatitis is linked to adenovirus,” a U.K. technical report from April 25 reads. “There may be a cofactor causing a normal adenovirus to produce a more severe clinical presentation in young children, such as increased susceptibility due to reduced exposure during the pandemic, prior SARS-CoV-2 or other infection, or a yet undiscovered coinfection or toxin. Alternatively, there may have been emergence of a novel adenovirus strain with altered characteristics.”

Similarly, the European CDC wrote in an April 28 risk assessment that “the current leading hypothesis is that a cofactor affecting young children having an adenovirus infection, which would be mild in normal circumstances, triggers a more severe infection or immune-mediated liver damage. Other aetiologies (e.g. other infectious or toxic agents) are still under investigation and have not been excluded but are considered less plausible.”

The WHO outbreak alert noted that adenovirus infection “does not fully explain the severity of the clinical picture,” since infection with adenovirus type 41, “the implicated adenovirus type, has not previously been linked to such a clinical presentation.” Adenoviruses, WHO explains, are quite common, but typically are self-limiting and cause respiratory or gastrointestinal symptoms, or sometimes conjunctivitis, or pink eye.

One possible reason for why children could be more susceptible to adenoviruses now could be because they were exposed to them less over the past several years as people spent more time apart during the pandemic. As a result, kids would have less immunity to adenoviruses.

“Factors such as increased susceptibility amongst young children following a lower level of circulation of adenovirus during the COVID-19 pandemic, the potential emergence of a novel adenovirus, as well as SARS-CoV-2 co-infection, need to be further investigated,” the report said, adding that both the U.K. and the Netherlands have reported increases in community adenovirus infections “following low levels of circulation earlier in the COVID-19 pandemic.”

Regardless of the cause, physicians encourage parents and children to wash their hands and practice good hygiene, which can help avoid the spread of adenoviruses as well as other infectious agents.