For months, experts have been trying to find out what is behind a number of unusual cases of hepatitis in children. Previously healthy children under the age of ten developed liver inflammation without any apparent cause. The complaints range from gastrointestinal problems and exhaustion to such a serious illness that a new liver had to be transplanted. The health authorities in more than 30 countries have been dealing with around 1,000 cases since spring. Now two research teams present a possible explanation. Accordingly, a double infection with two different viruses could play a role. Surprisingly, the Sars-CoV-2 coronavirus is currently not one of the suspects.
In the case of hepatitis, it makes sense to look for viruses that could be responsible for the inflammatory reaction in the liver. However, in the puzzling cases, it quickly became clear that the usual pathogens could be ruled out. They were not found in the sick children. Instead, scientists kept coming across adenoviruses. These are widespread pathogens that usually lead to mild illnesses with cold-like symptoms, vomiting and diarrhea. However, liver inflammation is “a known rare complication”, wrote the Robert Koch Institute at the end of April, after a first case from Germany became known. However, those with weakened immune systems are particularly affected by these severe courses. It was therefore speculated that the adenoviruses had changed and could now also be dangerous for children without an immune deficiency.
A gene variant in the genome of the affected children could also be involved
According to the two new studies, which are currently only available in preliminary versions and have not yet been peer-reviewed or published in scientific journals, adenoviruses may actually be involved in the puzzling cases of hepatitis. However, a second pathogen seems to be involved, the so-called adeno-associated virus 2 (AAV2) – a molecular free rider that cannot infect cells on its own, but always needs the help of other viruses to do so. So far, it has been assumed that AAV2 do not cause diseases. For this reason, they are also considered to be attractive delivery vehicles for gene therapy interventions that attempt to replace a defective gene in a person’s genome.
Now, two teams from the UK have independently found adeno-associated viruses in the affected children, along with either adenoviruses or herpesviruses. Sars-CoV-2 also appeared in a few cases. the smaller survey from Scotland led by Emma ThomsonProfessor of Infectious Diseases at the University of Glasgow, found AAV2 in all nine children examined with conspicuous hepatitis. The larger study led by virologist Judith Breuer from University College London examined 28 cases of hepatitis and found AAV2 in 94 percent, in large numbers in the vast majority of cases. In contrast, in control groups with children of similar age, hardly any AA2 was found, not even in children with liver inflammation that was due to an already clarified cause.
“It looks like co-infection is key to understanding these hepatitis cases,” says Deirdre Kelly, professor of pediatric hepatology at the University of Birmingham. “But it’s not yet clear why some children become so seriously ill that they need a transplant. Could there be another virus involved?” The answer could also lie in the genes. Both working groups found genetic variants particularly frequently in the hereditary disposition of the affected children, which normally occur much less frequently in the British population. Of the nine Scottish children, eight (89 percent) carried this particular variant of an immune system gene. Statistically, this variant can only be expected for 16 percent of the Scottish population.
The increase in cases could also be due to the protective measures against the corona pandemic that have ended
Judith Breuer and her team described the possible origin of liver inflammation as an immune reaction as a result of an infection with AAV2 and/or another virus in children with the corresponding hereditary factors. For the virologist Marco Binder from the German Cancer Research Center in Heidelberg, the fact that not all those affected may have the questionable genetic material is not an argument against this thesis. There could be many explanations for this.
Breuer and colleagues attribute the accumulation of hepatitis cases this spring to the protective measures against the corona pandemic that have ended. As a result, many children became infected for the first time with the very common pathogens, and with an unfavorable constellation between genes and co-infections, the conspicuous hepatitis numbers then occurred.
“My feeling tells me that there were already such cases of hepatitis before the pandemic,” Emma Thomson of the University of Glasgow told the British newspaper The Guardians. Due to the changes in the spread of the virus due to the corona protective measures, the otherwise sporadic cases have now occurred in large numbers. However, Marco Binder emphasizes that it is not necessarily a question of infections being left out as a result of the protective measures, “instead, a shift in the typical waves of infection from various pathogens can play a role”. This happened not only with adenoviruses, but also with influenza or RS viruses, which can cause serious problems for infants. “Such a shift in typical cycles has been observed around the world.”
Thomson and Breuer agree that there needs to be more and larger studies with more children to support their suspicions.