Scientist offers clues in mystery hepatitis outbreak in children

A British scientist investigating a mysterious global hepatitis outbreak that has infected hundreds of children globally believes researchers are getting closer to identifying its cause as more clues begin to emerge.

Judith Breuer, professor of virology and director of the pathogen genomics unit at University College London, was approached by the UK Health Security Agency to investigate a cluster of cases detected in Scotland last month.

She and a research team at Great Ormond Street Hospital in London are using metagenomics, the study of genetic material, to analyse which viruses are present in the RNA and DNA samples belonging to affected children in the hope it can offer insight into the source of the outbreak.

Although firm conclusions have yet to be made, adenovirus and immune systems weakened by coronavirus lockdowns are thought to be key factors.

What do we know so far?

At least 348 children around the world have been diagnosed with this new hepatitis, with some being forced to undergo liver transplants and some countries, such as Ireland and Indonesia, reporting a small number of deaths.

As of May 12, the HSA reported 176 confirmed cases of sudden onset hepatitis in under-10s in Britain. At least 11 of those have had liver transplants.

The cases are predominantly in children under 5, who showed initial symptoms of gastroenteritis, including diarrhoea and nausea, followed by the onset of jaundice.

None of the usual viruses that cause hepatitis (hepatitis viruses A to E) have been found in the children who have suffered from the recent cases.

What is the role of the adenovirus?

Many of the children who have fallen ill with the condition have tested positive for adenovirus, a typically harmless family of viruses that can cause illnesses ranging from conjunctivitis and pneumonia to the common cold.

Previous findings showed that 91 out of 126 children had adenovirus in their bloodstream.

Prof Breuer says her team is monitoring numerous different examples of adenovirus, including F41, a common type known to cause gastrointestinal problems in children, but which rarely develops into serious illness.

"It's difficult to know whether adenovirus is going around at the moment or if it is just an incidental finding," she told The National. "They're quite difficult to determine what type it is just from ordinary laboratory tests."

Other causes

Prof Breuer also indicated that the HHV-6, a herpes virus which infects young children and sometimes causes hepatitis, has been discovered in the liver samples and may be one of the competing explanations.

Another virus, known as AAV2 or adeno-associated virus has been found "at the highest levels" in all of the liver samples and some theories suggest that it is latent in the body until it is triggered by inflammation or a "catastrophic happening".

Researchers are also looking at whether the hepatitis is an abnormal immunological response within the children to these viruses. Prof Breuer said the cause could be either of these, or perhaps all of the above and that concrete answers remain frustratingly elusive.

Genetic sequencing has revealed that the hepatitis has not been caused by a novel virus, which Prof Breuer says is a welcome development.

Has Covid played a part?

Researchers have also looked at whether Sars-Cov-2, and in particular the Omicron variant, could be to blame for the outbreak of hepatitis in children.

Prof Breuer says Omicron's role is a "big question" but admitted "we don't have the answer".

Although many of the children have tested positive for Covid, metagenomic tests have seemed to play down an adverse reaction to Omicron as the main cause.

"We haven't found Omicron in our tests as a whole but it has certainly has been found in some children," Prof Breuer said. "We haven't found it from our metagenomics, for example. So at the moment, it remains uncertain what role it might in the in the genesis of this of this problem".

However, she does believe that social distancing resulting from coronavirus lockdowns may have resulted in lowered immune systems as viruses begin to circulate all at once.

"It's difficult to exclude the fact that this has happened now and it has not really been observed before," Prof Breuer said. "So I would speculate that something to do with the pandemic has actually affected this."

"It was such an upheaval, it's such as a schism in our lives. Who knows what impact that will have had on our immune systems and on the pathogens that are circulating?"

With vaccine scepticism still a widespread issue, Prof Breuer said the children are too young to have received their coronavirus shots and vaccination is not a line of inquiry.

What should parents do?

Prof Breuer said she was hopeful that the outbreak may have peaked and said that recent evidence showed the rate of increase in cases was falling.

However, she said she was unsure as to why Britain seems to be the epicentre of this outbreak as it accounts for nearly half of all global cases. Health authorities in Britain may have been more vigilant, Prof Breuer says, and expects the rest of the world will soon catch up.

In lieu of government advice, concerned parents have been urged to practise good hygiene and to seek medical advice if their children show symptoms of hepatitis, which include yellow or pale eyes and discoloured faeces.

"It's difficult to know what one would do without knowing what causes it," Prof Breuer said. "We're still trying to investigate what causes it and to take time and do the tests rigorously.

"I think the advice that has been given people is to practice good hygiene. We can't really say anything specific about what people should do to prevent it, we would not be correct in doing that."