Confused scientists are looking for the cause of the strange and alarming epidemic of severe hepatitis in young children, with 74 documented cases in the United Kingdom and three in Spain. Clinicians in Denmark and the Netherlands also report similar cases. And in the United States, the Centers for Disease Control and Prevention (CDC) announced late yesterday that it is investigating nine cases in Alabama.
Viruses can cause hepatitis, inflammation of the liver, but otherwise healthy children rarely get seriously ill. No children from the UK or Spain have died since April 12, but some are very ill: all have been admitted to hospitals and seven need liver transplants, six of them in the UK, according to a statement released today. Two of the nine affected children in Alabama required a liver transplant, the state Department of Public Health announced this afternoon.
The leading theory is that the culprit is adenovirus, a family of viruses that usually cause colds – up to half of children in the UK are positive for the virus, as are all children in Alabama. But so far the evidence is too thin to solve the mystery, researchers and doctors say.
“This is a serious phenomenon,” says Deirdre Kelly, a pediatric hepatologist at Birmingham Children’s Hospital in the United Kingdom. “These [were] perfectly healthy children… until a week ago. ” However, not all news is bad. “Most [the children] they recover on their own, ”Kelly notes.
“This should be taken seriously,” the WHO Regional Office for Europe wrote in a statement sent by e-mail. “The increase is unexpected, and the common causes are ruled out.”
Scottish investigators first identified the epidemic on March 31, when they alerted Scottish public health to a group of children aged 3 to 5 who were admitted to the Royal Children’s Hospital in Glasgow in the first 3 weeks of March. Everyone was diagnosed with severe hepatitis of unknown cause. Scotland typically has fewer than four such cases a year, investigators wrote in an article published yesterday. But as of April 12, there have been 13 cases of Scottish children, all but one in March and April.
Kelly, who works at one of England’s three centers for pediatric liver disease and transplantation, says her unit has seen 40 cases of childhood hepatitis of unknown cause since early this year. In the same period from January to April 2018, her unit saw only seven such children.
Most children in the UK are between 2 and 5 years old, according to a statement issued by the British Health Security Agency on 8 April. The European Center for Disease Prevention and Control issued a public warning on April 12 about an outbreak in the UK, noting that vomiting and jaundice – jaundice of the skin and sclera – are common symptoms.
Early hypotheses about what could make children sick involved exposure to toxins from food, drink or toys, but suspicion is now focused on the virus. None of the British or Spanish children had the hepatitis A, B, C or E virus, typical infectious causes of the disease. But a handful of children were positive for SARS-CoV-2 infection just before or after hospital admission; no one received the COVID-19 vaccine. In addition, as many as half had adenovirus, a common virus transmitted by respiratory droplets and contact with infected people or viruses on surfaces. It can cause vomiting, diarrhea, conjunctivitis and cold symptoms, but rarely causes hepatitis.
“Leading hypotheses focus on the adenovirus – either a new variant with a pronounced clinical syndrome or a routinely circulating variant that is more difficult to affect younger children who are immunologically naive,” the Scottish researchers wrote.
Isolation of the youngest children during a pandemic may have made them immunologically vulnerable because they were not exposed to a multitude of viruses, including adenoviruses, which usually affect infants. “We see an increase in typical childhood viral infections as children emerge from isolation, [as well as] an increase in adenoviral infections ”—but we can’t be sure one causes the other, says Will Irving, a clinical virologist at the University of Nottingham.
Researchers continue to study other possibilities. For example, the immune effects of a previous episode of COVID-19 could have made children more susceptible to infection, or the disease could be a long-term complication of COVID-19 itself. An unidentified toxin is also not excluded.
Not all cases may have a single cause, warns Jim McMenamin, an epidemiologist who heads the Scottish Public Health Infections Service. “It’s terribly important to make sure we’re looking for everything, not to just say it’s just one viral cause.”
In the United States, the CDC is assisting the Alabama Department of Public Health in investigating nine cases of hepatitis in children ages 1 to 6 who were also adenovirus-positive. The cases have occurred since October 2021, wrote Kristen Nordlund, a CDC spokeswoman in a statement sent to ScienceInsider last night.
“The CDC is working with state health departments to see if there are additional cases in the U.S. and what could be causing those cases,” she wrote. “Adenovirus may be the cause, but researchers are still learning more – including ruling out more common causes of hepatitis.”
Wes Stubblefield, a district medical officer with the Alabama Department of Public Health, said in an interview today that the last case in Alabama occurred in February and that five out of nine children are positive for adenovirus-41, a strain that usually causes gastroenteritis.
In Spain, meanwhile, the Madrid region government announced on April 13 that three regions – Madrid, Aragón and Castilla-La Mancha – had reported a case of severe hepatitis of unknown origin in young children. One child had a liver transplant.
Doctors at major pediatric liver centers in the Netherlands and Denmark said so ScienceInsider spotted similar trends yesterday. “There are children who are very ill and have been referred for a transplant,” says Ruben de Kleine, a pediatric liver transplant surgeon at the University Medical Center Groningen. “We estimated a similar number of children for transplantation in the first 4 months of 2022 [to what we] usually all year round. ”
And at the University Hospital in Copenhagen “we have more cases with [acute liver failure] than we normally have, ”says pediatric hepatologist Marianne Hørby Jørgensen. There are no children there who need a transplant.
Hørby Jørgensen and de Kleine point out that parents should not panic. To date, clinicians have identified a small number of cases in their countries where, together, more than 230,000 infants are born each year.
Updated, April 15, 3 p.m.: This story has been updated to include more details about the Alabama cases.