The Centers for Disease Control and Prevention is investigating 109 cases of severe hepatitis of unknown cause in children, officials said Friday. Five of the children have died.
Jay Butler, the CDC’s deputy director for infectious diseases, said the cases date back to October and were found in 24 states and one territory. More than 90% of the patients were hospitalized and 14% received liver transplants, he said. The majority have recovered, he said.
The cases, which have been discovered in at least 20 countries, continue to mystify scientists, who have been unable to pinpoint the cause. Officials say severe hepatitis in young children remains rare and urge parents not to panic but be on alert for unusual signs including jaundice — which causes yellowing of the skin and whites of the eyes — dark urine and light stool.
“Although rare, children can have serious hepatitis and it’s not uncommon for the cause to be unknown,” Butler said. He said there has not been a “significant increase” in the number of pediatric hepatitis cases or liver transplants, including before the pandemic.
A chief suspect is the adenovirus — a common family of some 50 viruses that cause symptoms ranging from colds and stomach upsets to pinkeye and, in rare cases, to conditions that affect the brain or spinal cord. About half the U.S. children whose hepatitis cases are under investigation had a confirmed adenovirus infection, Butler said, but officials do not yet know if it is the cause of the illnesses.
Officials said some of the more common causes of viral hepatitis — such as hepatitis A, B, C, D, and E — have not been found. Officials do not yet know what role other factors, such as environmental exposure, medications, or other infections might play in the illnesses.
“This is a very rare presentation of a common scenario,” said Helena Gutierrez, a pediatric gastroenterologist at Children’s of Alabama.
Nine children were diagnosed at the hospital between October and February, all of whom were previously healthy and had the adenovirus in their blood, officials said. Some of them had adenovirus 41, which typically causes stomach illness and can cause hepatitis in immunocompromised children — though none of the children in Alabama were immunocompromised, officials said.
“Kids get sick, they get viruses,” she said.
Gutierrez, who was involved in treating all nine cases, said there have been no cases since February at Children’s. Although two of the nine children needed liver transplants, all have recovered or are recovering.
CDC officials said the children sickened in Alabama had a median age of 2. None of them were infected with COVID-19 or had a history of having had COVID-19, officials said. Officials are working to determine through blood tests whether some of the children had prior unknown coronavirus infections.
None of the children in Alabama had received a coronavirus vaccine, officials said.
“COVID-19 vaccination is not the cause of these illnesses,” Butler said. “We hope that this information helps clarify some of the speculation circulating online.”
Butler said cases have been found in the following states and territories: 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.
As of May 1, the World Health Organization has recorded more than 220 cases in 20 countries in children ages 1 month to 16 years. An additional 50 cases are under investigation, according to a WHO media briefing Wednesday.
WHO officials said that notifications of new cases, together with more extensive searches, would lead to more cases being detected before the cause could be determined. Officials in Britain first alerted the WHO to cases of severe hepatitis in Scotland in early April; the CDC issued an alert on U.S. cases on April 21.
Officials urged clinicians to be alert for cases.
“Typically we don’t report cases of acute liver failure to any kind of public agency,” Gutierrez said. “Because it is under investigation, cases are going to come to the surface; people are going to be testing for adenovirus.”
Under normal circumstances, doctors may miss cases of adenovirus-related hepatitis, because with mild cases they don’t typically order up viral studies beyond looking for the common hepatitis A, B, or C, said Ryan Fisher, a pediatric gastroenterologist and transplant hepatologist at Children’s Mercy in Kansas City.
“It could be that we miss many cases of adenovirus-associated hepatitis in otherwise healthy kids because we don’t check for it and the children recover uneventfully,” Fisher said.
Doctors may now go back to earlier cases that resolved and check samples to see whether there is evidence of the virus, further boosting the numbers.
Leina Alrabadi, a pediatric gastroenterologist at Stanford Children’s Health, had a case of hepatitis in a 4-year-old in March and reported it a couple of weeks ago, after the CDC’s April 21 alert. That particular case did not result in liver failure.
“We’ve always had children that progress to transplant of unknown etiology,” Alrabadi said, adding that it’s too early to know what is causing the outbreak of severe cases.
Still, WHO scientists said they do not believe the adenovirus alone accounts for the severity of the liver inflammation. Investigators in the United Kingdom and elsewhere are looking into other factors, including whether young children have become more susceptible to the adenovirus after having less exposure during the pandemic; whether a novel adenovirus may have emerged; and whether co-infection with the coronavirus could be a factor, though that seems unlikely: Although some children tested positive for the coronavirus, according to the WHO, the infection rate is only slightly higher than in the general population.
Doctors advised seeing a pediatrician if children are exhibiting any unusual symptoms and said the pandemic reinforced the lessons of keeping kids safe from the adenovirus and other pathogens.
“Continue to enforce hand hygiene,” Gutierrez said, “before eating, after playing at the playground, and before touching a younger sibling who hasn’t been at school or day care.”