Double infection: possible cause found for mysterious hepatitis

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 have developed inflammation of the liver with no apparent cause. Complaints range from gastrointestinal problems and exhaustion to an illness so severe that a new liver had to be transplanted. Health authorities in more than 30 countries have been treating around 1,000 cases since the spring. Now two research teams present a possible explanation. Thus, a double infection by two different viruses could play a role. Surprisingly, the Sars-CoV-2 coronavirus is currently not among 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 confusing cases, it quickly became apparent that the usual pathogens could be ruled out. They were not found in sick children. Instead, scientists kept coming across adenoviruses. They are common pathogens that usually cause mild illness with cold symptoms, vomiting, and diarrhea. However, inflammation of the liver is “a known rare complication”, wrote the Robert Koch Institute at the end of April after the discovery of a first case from Germany. However, people with weakened immune systems are particularly affected by these severe developments. It was therefore hypothesized that the adenoviruses had changed and could now also be dangerous for children without immune deficiency.

A gene variant in the genome of 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According to the two new studies, which are currently only available in preliminary versions and have not yet been peer-reviewed or published in scientific journals, adenoviruses may in fact be involved in the puzzling cases of hepatitis. However, a second pathogen appears to be involved, the so-called adeno-associated virus 2 (AAV2) – a molecular free rider that cannot infect cells on its own, but still needs the help of others. viruses to do so. Until now, it has been assumed that AAV2 do not cause disease. For this reason, they are also considered attractive delivery vehicles for gene therapy interventions that attempt to replace a faulty gene in a person’s genome.

Now two teams in the UK have independently found adeno-associated viruses in affected children, as well as adenoviruses or herpesviruses. Sars-CoV-2 has also appeared in a few cases. The smallest Scottish study, led by Emma Thomson, professor of infectious diseases at the University of Glasgow, found AAV2 in all nine children examined with overt hepatitis. The larger study, led by virologist Judith Breuer of University College London, looked at 28 cases of hepatitis and found AAV2 in 94% of cases, in high amounts in the vast majority of cases. In contrast, in control groups with children of the same age, practically no AA2 was found, not even in children with inflammation of the liver due to an already clarified cause.

“It appears that co-infection is key to understanding these cases of hepatitis,” says Deirdre Kelly, professor of pediatric hepatology at the University of Birmingham. “But we don’t yet know why some children get so seriously ill that they need a transplant. Could there be another virus involved? The answer may also lie in the genes. Both working groups found particularly common genetic variants in the hereditary disposition of affected children, which normally occur much less frequently in the UK population. Of the nine Scottish children, eight (89%) carried this particular variant of an immune system gene. Statistically, this variant can only be expected for 16% of the Scottish population.

The increase in cases could also be due to the protective measures against the corona pandemic which have ended

Judith Breuer and her team have described the possible origin of liver inflammation as an immune reaction following infection by AAV2 and/or another virus in children carrying the corresponding hereditary factors. For virologist Marco Binder of the German Cancer Research Center in Heidelberg, the fact that not everyone involved has the dubious genetic material is no argument against this thesis. There could be many explanations for this.

Breuer and his colleagues attribute the accumulation of hepatitis cases this spring to the protective measures against the corona pandemic that have come to an end. As a result, many children were infected for the first time with the very common pathogens, and with an unfavorable constellation between genes and co-infections, the obvious numbers of hepatitis then occurred.

“My feeling is that there were cases of hepatitis like this before the pandemic,” Emma Thomson, from the University of Glasgow, told the British newspaper. The gardians. Due to changes in the spread of the virus due to corona protective measures, the otherwise sporadic cases have now occurred in large numbers. However, Marco Binder points out that these are not necessarily infections left behind as a result of protective measures, “on the contrary, a change in the typical waves of infection by various pathogens may play a role” . This has 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 need to be more and larger studies with more children to support their suspicions.


Leave a Comment