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Adenovirus remained the most likely underlying factor responsible for the outbreak of sudden onset hepatitis in children, UK public health experts have said.
Investigations are still ongoing into whether a cofactor could cause a normal adenovirus to produce a more severe clinical presentation, the UK Health Security Agency (UKHSA) said in an update on Monday.
A further three confirmed cases of acute non-A-E hepatitis in children with serum transaminases greater than 500 IU/L have been identified since the Agency’s last briefing on April 21, bringing the total number of known cases to 111. Of those, 81 were in England, 14 in Scotland, 11 in Wales, and 5 in Northern Ireland.
No deaths in the UK have occurred, but a total of 10 children affected subsequently received a liver transplant. Of the cases in England, 43 individuals had recovered.
Cases Mainly in Children Under 5
The cases have predominantly involved children under 5 years of age, although a small number of children aged 10 and older are being investigated, according to a technical briefing published by the UKHSA, which did not give further details because of patient confidentiality concerns.
Dr Meera Chand, director of clinical and emerging infections at UKHSA, said: “The cases in England are not known to be epidemiologically linked, they’re not contacts with each other, and they are dispersed all over the country.”
Dr Chand, who was speaking online to at a special session of the European Centre for Disease Prevention and Control congress in Lisbon, Portugal, added: “There’s a median age of the cases of 3 years old, who are very much still in that preschool age group, but the vast majority are in the 1 to 6 age band.”
Out of 53 of the cases tested for adenovirus, 40 were positive. Preliminary typing of the adenovirus was consistent with type 41F where data was available from blood samples, although other adenovirus types were identified in non-blood samples.
Routine NHS and laboratory data showed a current marked increase in adenoviruses compared with previous years, particularly in children aged one to four.
The UKHSA said whole genome sequencing was needed before the nature of the adenovirus involved in the spike in cases could be mapped, a process which could confirm or rule out one hypothesis that a novel adenovirus strain had emerged with altered characteristics. However, sequencing was currently proving a challenge because of low viral levels in the samples.
“I think our leading hypothesis, given the data that we’ve seen, would probably be that we have a normal adenovirus circulating,” said Dr Chand. “We may not have seen as much of it as we have for the past couple of years, but just one of the unknown viruses that we’re familiar with; but we have a co-factor affecting a particular age group of young children, which is either rendering that infection more severe or causing it to trigger some kind of an immunopathology.”
Could COVID be a Factor?
While the leading cause of the non-A-E hepatitis outbreak remained adenovirus, the Agency said investigations were examining possible co-factors, including increased susceptibility due to reduced exposure during the COVID-19 pandemic, prior infection with SARS-CoV-2, other infections, or toxins.
However, the high detection rates of SARS-CoV-2 was not unexpected, due to high prevalence in the community, the public health experts said. There was no current evidence that a new variant of SARS-CoV-2 might be implicated.
COVID-19 vaccines, travel, and hepatitis viruses A to E have so far been ruled out as possible factors.
The clinical syndrome often began with gastroenteritis-type symptoms, followed by the onset of jaundice.
Investigators in Scotland first identified the outbreak on March 31, when Public Health Scotland was alerted to a cluster of 3- to 5-year olds admitted to the Royal Hospital for Children in Glasgow with severe hepatitis of unknown aetiology within a 3-week period. “Really, this was just astute clinicians realising they were seeing something unusual,” said Dr Chand.
The World Health Organisation (WHO) was alerted on April 5, with the UK Government reporting further cases in England, Wales, and Northern Ireland on April 12.
Worldwide, at least 169 severe hepatitis cases in children aged between one month and 16 years have been identified in the current outbreak, the WHO said on Saturday. Among the cases, at least one child had died and 17 required liver transplants. The children have been between 1 month and 16 years old.
Commenting on the latest UKHSA briefing to the Science Media Centre, Deirdre Kelly, professor of paediatric hepatology at the University of Birmingham, said: “We still need to see evidence of a relationship with previous COVID infection, and whether the affected children are genetically or immunologically different from others, especially in relation to the adenovirus which may be a trigger rather than the causative factor.”
Créditos: Comité científico Covid