Less social mixing due to two years of covid restrictions may be a factor in an “unusual” and serious outbreak of acute liver disease among young children, scientists believe.
A total of 74 children in the UK, mostly under the age of five, have contracted a version of acute hepatitis which is not linked to normal strains of the disease, while dozens of cases have now been identified in the US, Europe and Israel. Six children in the UK have required liver transplant.
The UK Health Security Agency is expected to announce more cases shortly.
One line of inquiry by experts is a link to adenovirus, a common cold virus which can cause more serious symptoms including gastrointestinal illness in young children.
Cases of adenovirus in children were far lower than normal in 2020 and remained below the average in 2021, and experts believe it is “possible” that the lack of exposure to the virus in infants due to lockdown may have lowered their immunity, meaning they are suffering worse effects now that restrictions are lifted.
In a paper for the journal Eurosurveillance on 14 April, scientists investigating a cluster of serious hepatitis cases in Scotland said decreased social mixing may have played a part in suppressing immunity to adenovirus.
They said: “At the time of publication, the leading hypotheses centre around adenovirus – either a new variant with a distinct clinical syndrome or a routinely circulating variant that is more severely impacting younger children who are immunologically naïve.
“The latter scenario may be the result of restricted social mixing during the Covid-19 pandemic.”
Teams from the UK Health Security Agency, Public Health Scotland, and experts in Wales and Ireland have been investigating the outbreak as a matter of urgency, while the World Health Organisation, the US Centers for Disease Control and Prevention and the European Centre for Disease Prevention and Control are also investigating clusters in at least six more countries worldwide.
In Scotland, five out of the 13 hepatitis cases also tested positive for adenovirus. Five of the 13, two of whom had also had adenovirus, tested positive for covid-19.
Professor Graham Cooke, an expert in infectious diseases at Imperial College London, told i that both covid and adenovirus were in high circulation at the time the cases first emerged, adding: “We don’t know whether either [virus] is causing the problem or is just a bystander.”
He said the theory that younger children could be developing more serious symptoms due to lower immunity from lockdowns was “speculative but possible”.
He said: “It is speculative, but it’s definitely something that needs to be thought about. There is going to be a group of children under the age of two who have not been exposed to the same number of viruses that they would have been exposed to normally. It is speculative but it is possible.”
Prof Cooke said the illness was “clearly extremely serious, at least for some of them”.
One scientific source said adenoviruses do occasionally cause liver disease but it is usually in immunocompromised people.
A UKHSA source said health experts were not yet in a position to rule out any cause.
UK public health officials were first alerted to the outbreak in March, when Greater Glasgow and Clyde health board and the Scottish NHS reported that five children, aged three to five, had presented at the city’s children’s hospital with “severe hepatitis of unknown aetiology [cause] within a three-week period”.
This number in such a short space of time is rare: by contrast, the average number of cases of hepatitis in Scotland where the cause is not known is fewer than four over the course of a year.
Most of the children were aged three; seven were girls and six were boys. Most of the youngsters had jaundice, abdominal pain, nausea and tiredness before being admitted.
All of the children admitted were in hospital for at least six days. Five are still in-patients, while one has undergone a liver transplant.
None of the children had any significant history of illness and all were described as generally healthy before contracting the disease.
By last week, following the Scottish outbreak, the UKHSA revealed it was investigating a total of 74 cases across the UK: 49 in England, 13 in Scotland and the remainder in Wales and Northern Ireland.
Public health officials are also investigating “milder disease” of the liver in more children and some adults, according to Public Health Scotland.
While adenovirus is the lead suspect, investigating teams are still exploring other possible causes, and the link to covid-19 has not been ruled out.
Covid-19 has been known to affect internal organs of seriously ill patients, but this is rare among children.
The Public Health Scotland paper in Eurosurveillance says the cause could be “infection by an as yet uncharacterised SARS-CoV-2 variant” while “a novel or yet undetected virus also cannot be ruled out at this time”.
None of the children affected had been vaccinated for covid-19, meaning a link to the jabs has been ruled out.
GPs have been told to be aware of children “presenting acutely with gastrointestinal symptoms and jaundice or elevated serum transaminases [liver enzymes]”. Doctors should have a “higher index of suspicion and a lower threshold for referral for specialist care”, the Scottish paper says.
Any cases should be reported to national and international public health bodies for appropriate follow-up investigation and management.
While the outbreak was first identified in the UK, cases of acute hepatitis of unknown cause are now beginning to emerge globally.
Nine cases have been identified in children aged between 1 and 6 in Alabama, while there are infections in Denmark, Ireland, the Netherlands and Spain. On Wednesday, 12 cases were reported by health officials in Israel.
US health officials have said all nine cases in Alabama tested positive for adenovirus, with a possible link to one of the viruses of this family, adenovirus 41, which is associated with gut inflammation.
Parents are advised to be alert for symptoms of possible hepatitis, including jaundice, dark urine, itchy skin, muscle and joint pain, loss of appetite and a high temperature, and to contact a doctor immediately.