After two years spent poring over data to explain coronavirus, public health officials are now seeking to understand an unexpected rise in hepatitis cases in healthy children that are cropping up in a growing number of countries.
Canada and Japan this week joined more than a dozen other nations in reporting outbreaks as major health bodies, including the World Health Organization and the European Center for Disease Control and Prevention, launched investigations into the nearly 200 known cases.
Theories about the origins of the mystery illness, which is associated with severe liver inflammation and has led to at least 17 children requiring transplants, have proliferated since UK health authorities first raised the alarm in early April. One child has died so far, according to the WHO.
Many scientists hunting for the causes of the outbreak have focused on the role played by the coronavirus pandemic. Experts have hypothesized that the illness could be linked to a drop-off in immunity to adenovirus, a cause of the common cold, due to two years of pandemic-related restrictions, the after-effects of a coronavirus infection or even a mutated form of one of those viruses.
“Whatever theory you subscribe to, this has to stem from the huge public health event of the last two years,” said Alastair Sutcliffe, professor of general paediatrics at University College London. “It’s too much of a coincidence — either it’s a fall in immunity against adenovirus or the adenovirus is collaborating with Covid to cause hepatitis, but the pandemic has to play a role.”
Northern hemisphere countries have recorded a surge in common viruses — such as adenovirus, rhinovirus and chickenpox — since pandemic countermeasures were eased this winter, while also registering record-high Covid infection rates.
Will Irving, professor of virology at the University of Nottingham, said it was possible “the blank slate of immunity” left over by reduced social mixing, as countries locked down and schools closed, could make the effects of the adenovirus “more devastating”.
“It may be important early in life to meet a whole range of viruses and just get yourself sorted out, and that didn’t happen,” said Irving.
But scientists have warned against jumping to conclusions.
Adenovirus — a group of viruses typically associated with symptoms such as a persistent cough, conjunctivitis or diarrhoea — very occasionally causes hepatitis but almost never in healthy children.
“People are speculating till they’re blue in the face, but all we have is a heap of correlations and no certain cause,” said Isaac Bogoch, associate professor of medicine at the University of Toronto in Canada.
With the UK accounting for about three-fifths of the known cases, UK scientists are leading the way in investigating the illness. Of the 53 UK children tested for adenovirus, 40 returned positive results. But 16 per cent of the more than 100 UK cases also tested positive for Covid-19 upon admission, compared with a community infection rate of between 5 and 8 per cent over the same period.
“There are some clues but there’s a lot of scientific detective work still to be done,” said Deirdre Kelly, professor of paediatric hepatology at Birmingham Women’s and Children’s Hospital, which has treated the largest cluster of patients.
Philippa Easterbrook, a medical expert in the WHO’s global HIV, hepatitis and sexually transmitted infections programme, told a news conference this week the idea that adenovirus may have resulted in more severe infections because they had been suppressed during lockdown was “an interesting assessment of the data but it really needs to be followed up with more investigations”.
Covid-19 vaccinations have been ruled out as a possible cause, as the illness mainly affects children under 10 — few of whom have received jabs.
The first known cases of the mystery hepatitis were recorded in the US state of Alabama between November 2021 and February this year. Five of the nine children tested positive for adenovirus, while none of them showed signs of current or prior Covid infection. Last week, the US Centers for Disease Control and Prevention issued an alert about the illness and seven states are now investigating possible cases.
“When . . . this was presented to me, I said I’d not seen a cluster like this in my career,” said Dr Karen Landers, chief medical officer for the Alabama Department of Health, who has worked in public health for more than four decades.
Professor Jeffrey Lazarus, head of the Health Systems Research Group at the Barcelona Institute for Global Health, said the “long list” of symptoms associated with Covid-19 suggests a prior coronavirus infection could be involved. “There’s been a whole host of Covid symptoms. It wouldn’t totally surprise me if an extra one was added,” he said.
Experts believe that a prior Covid-19 infection could weaken the immune system, prompting a more severe reaction to the adenovirus.
In the UK, genomic sequencing analysis is being carried out on adenovirus samples from patients to determine whether the virus has taken on mutations that could lead to hepatitis. Covid antibody testing is also under way.
However, Lazarus cautioned against some experts “jumping the gun based on what their thoughts about Covid restrictions were”. “The commentary is ahead of the science. Let’s give time for the science to catch up.”