Is a common virus the cause of an unexpected, unusual surge in hepatitis and liver failure in children, which has spread to more than 20 countries, and with possible cases totalling just under 350 – of which 15 children needed transplants and at least five have died, writes Sarah Zhang in The Atlantic.
Most of the initial cases affected children under five years old, with severe, unusual liver failure: symptoms have been typical: skin and eyes yellow with jaundice, markers of liver damage off the charts.
In the first case, in Alabama, while the girl was tested for all the usual liver disease suspects, the only positive test was, surprisingly, for adenovirus – a common virus causing mild colds, pink eye, or stomach flu. Rarely, it’s linked to hepatitis, or inflammation of the liver, in immunocompromised patients. But this girl had been healthy.
Then it happened to a second child, with the same symptoms, who again positive for adenovirus. “One patient is a fluke; two is a pattern,” says Markus Buchfellner, a paediatric-infectious-disease doctor at the University of Alabama at Birmingham (UAB). Two quickly became three and then four. Alarmed, the doctors alerted authorities and the US Centers for Disease Control (CDC), whose investigation ultimately found nine such cases of unusual hepatitis in kids in Alabama. Two needed liver transplants.
Then UK investigators discovered over their own increase in paediatric hepatitis, since identifying more than 150 cases.
Early evidence pointing to a link with adenovirus was too strong to dismiss and not strong enough to close the case: 70% of the cases have tested positive for adenovirus, says the WHO, which issued a global alert two weeks ago, saying that while mild paediatric hepatitis is not unheard of, severe hepatitis in previously healthy children is rare. The latest cases have affected children aged from one month to 16 years old.
But although some biopsies have been conducted, they have failed to find adenovirus in the kids’ livers. However, it’s known that a different virus infected a number of children recently: SARS-CoV-2. Yet the correlation here is even murkier; only 18% of the probable cases tested positive for COVID.
The leading hypotheses suggest an interaction between adenovirus and COVID, either because social distancing changed the patterns of adenovirus immunity, allowing for more severe or simply more adenovirus infections, or because previous infection or co-infection with the coronavirus triggers an unusual response to adenovirus. Alternatively, did the adenovirus itself change, evolving to more readily damage the liver?
The only culprit that can be conclusively ruled out is COVID vaccines, because under 5s, the bulk of the hepatitis cases, cannot be vaccinated. So experts are examining key data.
Have these kids had COVID before? Most tested negative, but investigators are checking whether any had COVID previously, and is the virus really playing a role? If so, kids with hepatitis are more likely to have COVID antibodies than a control group who did not.
Adenoviruses are common, so could the positive tests simply reflect incidental infections unrelated to liver failure?
Investigation will also focus on the adenoviruses in these samples. Sequencing their genomes can determine whether the viruses recently acquired new mutations, explaining the link to liver failure. This type of virus is adept at reshuffling its genome.
Partial sequencing of the viral genome, though, has already pinpointed one particular type of adenovirus in the cases: adenovirus 41, or 41F.
Although adenovirus has been linked to severe liver failure, it’s never been adenovirus 41 but types 1, 2, 3, 5, and 7. Perhaps it somehow triggers the immune system to start attacking the liver, either by itself or in combination with another virus, toxin, or environmental factor. And this might continue even after the virus itself is cleared, so tests for adenovirus could turn up negative.
This means finding the answer to these cases won’t be straightforward. But determining whether these kids have also had COVID, whether their adenovirus infections are incidental, and whether their viruses have mutated, should partially reduce the list of hypotheses.
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