Researchers today insisted that Covid itself is not responsible for a mysterious hepatitis outbreak affecting children around the world.
However, pandemic-era lockdowns may have played a role.
Scientists today named a normally harmless virus as the main culprit in a rare liver disease, which has sickened 200 young people in the UK and left a dozen needing transplants.
Two separate studies concluded that adeno-associated virus 2 (AAV2) plays an ‘important role’.
The virus, which usually causes no illness, affects most Britons by the age of 10.
But AAV2 cannot replicate without a ‘helper’ pathogen, such as adenovirus – which normally only causes cold-like symptoms. Adenoviruses increased according to the hepatitis cluster, which experts believe is because children’s immune systems were weakened when they returned to pre-pandemic levels.
Therefore, a team of academics supported by the UK Health Security Agency believe that dual infection with these two viruses may offer the best explanation for the outbreak.
Until now, scientists have been hesitant about the exact cause of the disease, theoretically blaming Covid itself or even a mutation in the adenovirus strain.
Q&A: What is the mysterious global hepatitis epidemic and what is behind it?
What is hepatitis?
Hepatitis is an inflammation of the liver that is usually caused by a viral infection or liver damage from drinking alcohol.
Some cases resolve on their own without any ongoing problems, but a fraction can be life-threatening, requiring patients to undergo a liver transplant to survive.
What are the symptoms?
People who have hepatitis usually have fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, and joint pain.
They may also suffer from jaundice – when the skin and whites of the eyes turn yellow.
Why are experts worried?
Hepatitis is usually rare in children, but experts have already seen more cases in a year than would normally be expected in the current outbreak.
According to the World Health Organization, the cases are of ‘unknown origin’ and are severe.
What are the top theories?
Adeno-associated virus 2 (AAV2)
Two separate UK studies, which looked at dozens of children across the country, found that adeno-associated virus 2 (AAV2) was behind the hepatitis disease.
The virus, which doesn’t usually make people sick, often causes a flu-like illness with adenovirus infections.
British experts working to investigate the spread of the disease believe that the endless cycle of lockdowns has played a major role.
Restrictions due to reduced social interaction can weaken children’s immunity, making them more vulnerable to adenovirus.
This means that ‘normal’ adenovirus can also cause serious consequences, as children are not responding to it as they used to in the past.
Other scientists said it may be an adenovirus that has acquired ‘unusual mutations’.
This would mean that it may be more transferable or able to capture the children’s natural immunity.
Overall, the two studies, which looked at dozens of children across the UK, found that 96 per cent of children with unexplained hepatitis had ‘high levels’ of AAV2.
By comparison, only four percent of healthy young adults tested positive for AAV2, and at much lower levels.
The study’s lead author, Dr Antonia Ho, said the Covid lockdown and restrictions ‘drastically reduced the circulation of the seasonal virus’.
He said a ‘balance’ needed to be re-established as young people were mixing in pre-pandemic ways, leading to ‘different types circulating’ of the virus.
Sufferers of the strange disease are mainly people under the age of five who initially experience diarrhoea, vomiting and abdominal pain, followed by jaundice – yellowing of the skin.
Some are then hospitalized with liver inflammation one to 11 weeks later, with 40 percent being admitted to intensive care.
The World Health Organization (WHO) has reported at least 1,010 cases in 35 countries. Worldwide, about 50 have required a liver transplant and 22 have died.
The preprints, which have not yet been peer-reviewed but have been published on the website MedRxiv, suggest that AAV2 is involved in the outbreak of hepatitis.
The first study, led by the MRC-University of Glasgow Center for Virus Research (CVR), examined nine children in Scotland with hepatitis, an average age of four.
They were all admitted to hospital between March 14 and April 4 and stayed in NHS care for an average of 10 days. A liver transplant is not required.
Their DNA was extracted from blood, liver, stool and throat samples and the results compared to 58 healthy young adults.
AAV2 was detected in all nine hepatitis patients but in none of the control groups.
In a separate analysis, the researchers examined the genetics of hepatitis patients.
They found that nine in 10 young people with hepatitis (89 percent) had the human leukocyte antigen gene, compared with two in 10 (16 percent) in the general population.
The team said the finding could offer another part of the answer to why some children become seriously ill.
Professor Emma Thompson, clinical professor and consultant in infectious diseases at CVR and senior author of the Scottish study, explained: ‘The gene itself is important because it encodes a receptor that presents viruses or other pathogens to the immune system.
‘And so this suggests that there may be an immune-mediated connection to virus-induced hepatitis.’
However, he said more studies are needed to confirm the gene’s involvement.
The second study, led by Great Ormond Street Hospital (GOSH) and the UK Health Security Agency, looked at 28 children in the UK with hepatitis.
Their analysis included liver samples from five children who needed transplants and blood samples from the remaining teenagers who did not.
Almost all children tested positive for AAV2. By comparison, AAV2 was ‘only very rarely’ present outside this group – in only six per cent of healthy children and at ‘very low levels’.
And sequencing of liver samples showed that AAV2 was present and spread within the organ.
Both studies ruled out that recent or previous Covid infection caused the hepatitis.
Tests showed that only two-thirds of those with hepatitis had antibodies to Covid – which was widespread among Scottish children at the time – and none of the liver samples contained the virus. None of the youths had the covid vaccine.
Researchers still don’t know why the hepatitis epidemic is spreading now.
However, he said a peak of adenovirus infections in the general population after the lockdown is ‘possible’.
Scientists have long warned that curbing the spread of the virus also prevented other infections from circulating in the population, weakening people’s immunity against them.
AAV2 itself may be the cause, or it may be acting as a ‘useful biomarker’ of recent adenovirus infection, which may be behind cases of hepatitis, Professor Thompson said.
He said: ‘There are many unanswered questions and larger studies investigating the role of AAV2 in pediatric hepatitis cases are urgently needed.
‘We also need to understand more about the seasonal circulation of AAV2, a virus that is not routinely monitored – it may be that AAV2 exposure coincides with peaks in adenovirus infections,’ Due to which, in susceptible young children, hepatitis occurs abnormally. .’
Professor Judy Brewer, a virologist at GOSH, said the findings were ‘reassuring to parents concerned about Covid as neither team found a direct link to SARS-CoV-2 infection’.
‘Our data, however, point to AAV2 in the liver and, or blood of cases, as the strongest biomarker for hepatitis,’ he added.