Children are silhouetted against a pond at a park in Lenexa, Kansas on Dec. 26, 2020. Health officials remain baffled by mysterious cases of severe liver damage in hundreds of young children around the world. (Charlie Riedel, Associated Press)
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NEW YORK – Health officials remain perplexed by mysterious cases of severe liver damage in hundreds of young children around the world.
The best available evidence points to a fairly common stomach bug that is not known to cause liver problems in otherwise healthy children. This virus was detected in the blood of affected children but, surprisingly, it was not found in their diseased livers.
“There are a lot of things that don’t make sense,” said Eric Kremer, a virus researcher at the Institute of Molecular Genetics in Montpellier, France.
As health officials from more than a dozen countries investigate the mystery, they ask:
- Has there been an increase in the stomach virus – called adenovirus 41 – which is causing more cases of a previously undetected problem?
- Are children more vulnerable because of pandemic-related lockdowns that have protected them from the viruses that children usually fall victim to?
- Is there a mutated version of the adenovirus causing this? Or another germ, drug or toxin not yet identified?
- Is it some kind of haywire immune system reaction triggered by prior COVID-19 infection and subsequent invasion by another virus?
The US Centers for Disease Control and Prevention and investigators around the world are trying to figure out what’s going on.
The diseases are considered rare. Last week, CDC officials said they are currently reviewing 180 possible cases across the United States. Most of the children were hospitalized, at least 15 required liver transplants and six died.
More than 20 other countries have reported hundreds of additional cases in total, although the highest numbers have been in the UK and the US.
Symptoms of hepatitis – or inflammation of the liver – include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, pale stools, joint pain and jaundice .
There are a lot of things that don’t make sense.
– Eric Kremer, Institute of Molecular Genetics
The extent of the problem only began to become clear last month, although disease sleuths say they have been working on the mystery for months. Finding a cause has been extremely difficult, experts say.
The conventional causes of liver inflammation in otherwise healthy children – the viruses known as hepatitis A, B, C, D and E – have not been detected in the tests. Also, the kids came from different places and there didn’t seem to be any common exhibits.
What emerged was adenovirus 41. More than half of US cases tested positive for adenovirus, of which there are dozens of varieties. In a small number of samples tested to see what type of adenovirus was present, adenovirus 41 appeared every time.
The fact that the adenovirus continues to appear strengthens the case for its role, but it’s unclear how, Dr. Jay Butler, the CDC’s deputy director for infectious diseases, told The Associated Press.
Many adenoviruses are associated with cold symptoms, such as fever, sore throat, and pink eye. Some versions – including adenovirus 41 – can trigger other problems, including inflammation of the stomach and intestines. Adenoviruses have been linked to hepatitis in children in the past, but especially in children with weakened immune systems.
Recent genetic analysis found no evidence that a single new mutant version of the virus was to blame, said Dr. Umesh Parashar, head of the CDC group focused on viral bowel diseases.
Adenovirus infections are not routinely tracked in the United States, so it is unclear if there has been a recent increase in viral activity. In fact, adenoviruses are so common that researchers aren’t sure what to make of their presence in these cases.
“If we start testing everybody for adenovirus, they’ll find so many kids” who have it, said Dr. Heli Bhatt, a pediatric gastroenterologist who treated two Minnesota children with liver problems. .
One was a child who arrived nearly five months ago with liver failure. Doctors couldn’t figure out why. Unfortunately, “having no cause is something that happens,” Bhatt said. About a third of cases of acute liver failure remain unexplained, experts have estimated.
Bhatt said the second child she saw fell ill last month. By then, health officials had drawn attention to the cases, and she and other doctors began to go back and review unexplained illnesses since October.
Indeed, many of the cases added to the tally in recent weeks were not recent illnesses but rather earlier illnesses that were reassessed. About 10% of US cases occurred in May, Butler said. The rate appears to have been relatively stable since the fall, he added.
It’s possible doctors are simply discovering a phenomenon that’s been going on for years, some scientists have said.
Another possible explanation: COVID-19.
The CDC recently estimated that in February, 75% of American children had been infected with the coronavirus.
Only 10% to 15% of children with the mysterious hepatitis had COVID-19, according to nasal swab tests taken when they were checked into the hospital, health officials said.
But investigators are questioning previous coronavirus infections. It’s possible that coronavirus particles lurking in the gut are playing a role, said Petter Brodin, a pediatric immunologist at Imperial College London.
In a paper published earlier this month in the medical journal Lancet, Brodin and another scientist suggested that a combination of persistent coronavirus and adenovirus infection could trigger a liver-damaging immune system response.
“I think it’s an unfortunate set of circumstances that could explain this,” Brodin told the AP.
Butler said researchers have seen such complex reactions before, and investigators are discussing ways to better test the hypothesis.
He said it was “not at all out of the realm of plausibility”.
A preprint study from Case Western Reserve University, which has not yet been peer-reviewed, suggested that children with COVID-19 had a significantly higher risk of liver damage.
Dr. Markus Buchfellner, a pediatric infectious disease physician at the University of Alabama at Birmingham, helped identify the first US cases in the fall.
The illnesses were “strange” and concerning, he said. Six months later, “we don’t really know what we’re dealing with”.