Among them, 14% needed a transplant and five children died.
Almost all of the children – more than 90% – required hospitalization.
Dr. Jay Butler, deputy director of infectious diseases at the CDC, stressed that the investigation — a partnership between the CDC and state health departments — is an evolving situation. All the cases of hepatitis they are currently investigating may not all be caused by the same thing.
“It’s important to note that this is an evolving situation, and we’re casting a wide net to help broaden our understanding,” Butler said.
Hepatitis, or liver swelling, can be caused by infections, autoimmune diseases, medications and toxins. A family of viruses well known for attacking the liver causes hepatitis A, hepatitis B and hepatitis C.
It is not known what motivates these cases in young children. Butler said some of the common causes of viral hepatitis were considered but were not found in any of the cases.
Adenovirus was detected in more than 50% of cases, although its role is unclear.
First reports of hepatitis
He asked doctors and public health officials to let the agency know if they had similar cases of children under 10 with elevated liver enzymes and no apparent explanation for their hepatitis dating back to October.
Since then, health departments have been working with pediatric specialists in their states to identify possible cases. The figures shared at Friday’s press conference are the first national look at the cases.
Cases are under investigation in 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.
Most children were healthy when they developed symptoms such as fatigue, loss of appetite, vomiting, diarrhoea, abdominal pain, dark urine, pale stools and yellowing of the skin and eyes – a sign called jaundice.
Unusually severe liver inflammation
Pediatric gastroenterologist Dr. Heli Bhatt of M Health Fairview Masonic Children’s Center in Minneapolis treated two children who are part of the CDC’s investigation. One of them, a 2-year-old child from South Dakota, underwent a liver transplant this week.
Bhatt says liver failure in children is “super rare.” And even before scientists started tracking this outbreak, half of the cases were never explained.
Doctors who treated these children say their cases stood out.
“Even on the first case, I thought it was weird,” says Dr. Markus Buchfellner, a pediatric infectious disease specialist at the University of Alabama at Birmingham, where staff started seeing cases in october.
“And then when the second one came, that’s when I said, ‘OK, we need to talk to someone about this. He contacted senior physicians in his department, who contacted the state health department and the CDC.
Buchfellner says the cases stood out because the liver inflammation was so severe.
Sometimes common viruses like Epstein-Barr or even SARS-CoV-2 raise a child’s liver enzymes a little, indicating what Buchfellner calls “little bits of hepatitis,” but children usually recover when their body fights infection.
“But it’s very strange to see a healthy child come in with the amount of liver damage these children had,” he said.
Initially, UAB saw nine children with unexplained hepatitis, and all nine tested positive for adenovirus in their blood. None of them tested positive for Covid-19 while in hospital or had a documented history of Covid-19, Butler said at the press conference.
Since these cases were reported, two more children in Alabama have been identified. Their cases are being investigated, bringing the state’s total to 11, said Dr. Wes Stubblefield, physician in charge of Alabama’s northern and northeast districts.
There are about 100 types of adenovirus. Around 50 of them are known to infect humans, so experts had to take a closer look at the virus to try to determine if all children had the same one.
When researchers tried to read adenovirus genes from infected children, only five had enough genetic material to get a full sequence. In all five cases, the virus was a special type called adenovirus 41. It usually causes diarrhea and vomiting in children, sometimes with congestion or coughing, but has never been associated with liver failure in children by elsewhere in good health.
Butler said Friday that adenoviruses 40 and 41 have been linked to hepatitis but almost exclusively in immunocompromised children.
Clues from the UK
Also on Friday, researchers from the UK Health Security Agency released a new technical briefing with an update on its hepatitis investigation. Of 163 cases, 126 patients were tested for adenovirus and 91, or 72%, were positive for this pathogen.
Investigators attempted to sequence the entire genome of an adenovirus from one of the patients, but were unable to obtain a sample containing enough virus to do so. There were 18 cases in which they were able to partially sequence the genome, and all of them were adenovirus 41F, the same one found in the US cases.
Many have wondered if the cases could somehow be linked to SARS-CoV-2, the virus that causes Covid-19.
British investigators say they are still investigating the possibility, but only 24 of the 132 patients tested – 18% – detected SARS-CoV-2.
The report says they do not rule out a role for Covid-19 infection in these cases. Perhaps a prior Covid-19 infection somehow primed the immune system to make these children unusually susceptible, or perhaps a co-infection of the two viruses together is overwhelming the liver.
Researchers also want to know if hepatitis is part of a kind of syndrome that strikes children after SARS-CoV-2 infection, such as the rare complication called multisystem inflammatory syndrome in children, or MIS-C.
Another working theory from UK investigators is that there is some sort of overblown or erratic immune response in these children, possibly because they have been shielded more than usual during the pandemic.
Yet another theory is that the adenovirus may have always caused liver failure in a tiny percentage of infected children, and these rare cases only come to light because they cause an unusually large wave of infections.
And investigators in the UK say they are still testing for drugs, toxins or possibly environmental exposure, although some sort of infection is probably more likely to be the cause.
Sorting out the role of adenovirus 41
Another thing that puzzles doctors, Buchfellner says, is that they found adenoviruses in blood samples, but not in liver tissue samples taken during biopsies from patients in Alabama.
“All nine have liver biopsies which showed a lot of inflammation and hepatitis. But we didn’t find the virus in the liver. We only found the virus in the blood,” he said. he declares.
The case of Bhatt, a child from South Dakota, was also positive for adenovirus in her blood but not in her liver.
If adenovirus 41 is somehow responsible in these cases — and it’s still a big if — Buchfellner says he doesn’t know why it would only show up in the blood but not in heavily damaged liver tissue. But he has theories.
“Perhaps the liver clears the virus before it’s cleared in the blood,” he said. “And so by the time the damage has been done to the liver and we do the biopsy, the immune system has already cleared the virus from the liver. And what’s left is just inflammation.”
His second theory is that it is not the virus itself that is responsible for the liver damage, but perhaps the immune system overreacts when trying to fight off the virus and ends up damaging the liver.
Adenovirus infections are common, so perhaps finding the virus in some of these patients was just a coincidence. “We’re not 100% sure it’s just this adenovirus. There’s still a lot to know,” Bhatt said.
Butler said Friday that experts are considering a range of possibilities, including exposure to animals.
“We are really casting a wide net and keeping an open mind about whether adenovirus data may reflect an innocent bystander or whether there may be co-factors that make adenovirus infections manifest in ways that don’t. ‘hasn’t been commonly seen before,’ he mentioned.
Investigators say they know this news may worry parents.
Butler says investigators still believe these cases are very rare. They did not find an increase, for example, in the number of children presenting to the emergency room with hepatitis.
“We always say to at least our families here in Alabama — and I encourage other families the same way — not to worry too much about it just yet.” said Buchfellner. “I mean, at the end of the day, it’s still a pretty rare phenomenon.”
Buchfellner says adenoviruses are commonly transmitted in daycares and schools. They usually don’t cause anything worse than something like a stomach flu for a few days.
“It’s been around for a long time, and it’s going to keep circulating. And in total, we only have about 200 cases that have been reported across the world. So it’s not a Covid pandemic type situation where everything the world needs to be really concerned about this,” he said.