“There’s a lot that doesn’t make sense,” said Eric Kramer, a virus researcher at the Institute of Molecular Genetics in Montpellier, France.
As health officials in more than a dozen countries look into the mystery, they ask:
- Is there an increase in stomach bugs called adenovirus 41 – which is causing more problems with previously undiagnosed problems?
- Are children more susceptible to epidemic-related lockdowns that protect them from the viruses that children are usually exposed to?
- Is some modified version of adenovirus causing this? Or something else that has not yet been identified as a germ, drug or toxin?
- Is it a reaction of the immune system to a previous Covid-19 infection and a subsequent attack by another virus?
The US Center for Disease Control and Prevention and investigators around the world are trying to find out what is happening.
Illness is considered rare. CDC officials said last week that they were now looking into 180 possible cases across the United States, most of which involved children being hospitalized, requiring at least 15 liver transplants and six deaths.
More than a hundred other cases have been filed in more than 20 other countries, although the highest numbers have been in the United Kingdom and the United States
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 extent of the problem began to become clear last month, although disease detectives say they have been working on the mystery for months. Experts say it is very difficult to find a cause.
Other common causes of hepatitis A in healthy children – viruses known as hepatitis A, B, C, D and E – have not been tested. What’s more, the children came from different places and there seems to be no general exposure.
What has been seen is adenovirus 41. More than half of the cases in the United States have tested positive for adenovirus, including dozens of types. By testing a small number of samples to see what type of adenovirus was present, adenovirus 41 came up each time.
While the adenovirus appears to be strengthening the case for a role to play, the CDC’s deputy director for the infectious disease, Dr. J. Butler, told the Associated Press how it plays out.
Many adenoviruses are associated with common cold symptoms such as fever, sore throat and pink eyes. Some versions – including adenovirus 41 – can trigger other problems, including inflammation of the stomach and intestines. Adenoviruses were previously associated with hepatitis in children, but mostly in children with weakened immune systems.
Recent genetic analysis has found no evidence that a single new mutant version of the virus is responsible, said Dr. Umesh Parashar, head of the CDC Group, which focuses on viral intestinal diseases.
Adenovirus infections are not systematically tracked in the United States, so it is not clear if there has been any recent increase in virus activity. In fact, adenoviruses are so common that researchers aren’t sure what their presence will be in this case.
“If we start testing everyone for adenovirus, they will find many children who have it,” said Dr. Haley Watt, a pediatric gastroenterologist who treated two Minnesota children with liver problems.
A child came to the country with liver failure about five months ago. Doctors did not understand why. Unfortunately, “something that doesn’t have a cause happens,” Bhatt said. About one-third of acute liver failure cannot be explained, experts estimate.
Bhatt said the second child he saw fell ill last month. By then, health officials were focusing on the cases, and he and other doctors had been returning since October to review the unexplained illnesses.
In fact, adding to the numbers in the last few weeks was not a recent illness in many cases, but rather the ones that were re-evaluated. About 10% of incidents in the United States occurred in May, Butler said. The rate seems to be relatively flat since the fall, he added.
It is possible that doctors are merely discovering a phenomenon that has been going on for years, some scientists say.
Another possible explanation: COVID-19.
The CDC recently estimated that, as of February, 75% of children in the United States were infected with the coronavirus.
Health officials say only 10% to 15% of children with mysterious hepatitis had Covid-19 when they took a nasal swab test while checking in at a hospital.
However, investigators are considering a previous coronavirus infection. It is possible that coronavirus particles lurking in the gut are playing a role, says Peter Brodin, a pediatric immunologist at Imperial College London.
Earlier this month, in a report in the medical journal Lancet, Brodin and another scientist suggested that a combination of chronic coronavirus and adenovirus infections could trigger a liver-damaging immune system response.
“I think it’s an unfortunate combination of situations that could explain it,” Brodin told the AP.
Butler says researchers have seen similarly complex reactions before, and investigators are discussing ways to better test the hypothesis.
He said it was “not out of the question.”
A case Western Reserve University preprint study, which has not yet been peer-reviewed, suggested that children who had Covid-19 had a significantly higher risk of liver damage.
Dr. Marcus Buchfelner, a pediatrician at the University of Alabama
The fall involved the first U.S. case detection.
Illnesses are “weird” and related, he said. Six months later, “we don’t really know what we’re working on.”