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. That virus was detected in the the blood of stricken children but — oddly — it has not been found in their diseased livers.
“There’s a lot of things that don’t make sense,” said Eric Kremer, a virus researcher at the Institute of Molecular Genetics of Montpellier, in France.
As health officials in more than a dozen countries look into the mystery, they are asking four main questions:
Has there been some surge in the stomach bug — called adenovirus 41 — that is causing more cases of a previously undetected problem?
Are children more susceptible due to lockdowns related to COVID-19 that sheltered them from the viruses children usually experience?
Is some mutated version of the adenovirus causing this, or some other not-yet-identified germ, drug or toxin?
Is it some kind of haywire immune system reaction set off by a past COVID-19 infection and a later invasion by some other virus?
The US Centers for Disease Control and Prevention (CDC) and investigators around the globe are trying to discover what is going on.
The illnesses are considered rare.
CDC officials last week said they are now looking into 180 possible cases across the US.
Most of the children were hospitalized, at least 15 required liver transplants and six died.
More than 20 other countries have reported hundreds more cases in total, although the largest numbers have been in the UK and US.
Symptoms of hepatitis — or inflammation of the liver — include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, joint pain and jaundice.
The scope of the problem only started to become clear last month, although disease detectives say they have been working on the mystery for months.
It has been maddeningly difficult to nail a cause down, experts say.
Conventional causes of liver inflammation in otherwise healthy children — the viruses known as hepatitis A, B, C, D and E — did not show up in tests. What is more, the children came from different places and there seemed to be no common exposures.
What did show up was adenovirus 41. More than half of the US cases have tested positive for adenovirus, of which there are dozens of varieties. In a small number of specimens tested to see what kind of adenovirus was present, adenovirus 41 came up every time.
That adenovirus keeps showing up strengthens the case for it playing a role, but it is unclear how, said Jay Butler, the CDC’s deputy director for infectious diseases.
Many adenoviruses are associated with common cold symptoms, such as fever, sore throat and pink eye. Some versions — including adenovirus 41 — can trigger other problems, including inflammation in the stomach and intestines.
Adenoviruses have previously been linked to hepatitis in children, but mostly in those with weakened immune systems.
Adenovirus infections are not systematically tracked in the US, so it is not clear if there has been some recent surge in virus activity. Adenoviruses are so common that researchers are not sure what to make of their presence in these cases.
It is possible that doctors are merely discovering a phenomenon that has been going on for years, some scientists said.
Another possible explanation is COVID-19.
The CDC recently estimated that, as of February, 75 percent of US children had been infected by the coronavirus.
Only 10 percent to 15 percent of the children with the mysterious hepatitis had COVID-19, according to nasal swab tests given when they checked into a hospital, health officials say.
However, investigators are wondering about previous coronavirus infections. It is possible that coronavirus particles lurking in the gut are playing a role, said Petter Brodin, a pediatric immunologist at Imperial College London.
In a piece earlier this month in the medical journal Lancet, Brodin and another scientist suggested that a combination of lingering coronavirus and an adenovirus infection could trigger a liver-damaging immune system reaction.
“I think it’s an unfortunate combination of circumstances that could explain this,” Brodin said.
Butler said researchers have seen complex reactions like that before, and investigators are discussing ways to better check out the hypothesis.
He said it was “not out of the realm of plausibility, at all.”
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