Since last fall, doctors at the Children’s Hospital of Alabama have been wrestling with a mystery. From October 2021 to February this year, nine children – the youngest aged 20 months and the oldest aged 5 years and 9 months – were rushed to hospital with worrying symptoms, all of which resolved. found to be due to unexplained cases of acute hepatitis, also known as inflammation of the liver.
As recently reported by the US Centers for Disease Control and Prevention (CDC), all patients tested negative for hepatitis A, B, and C viruses, and also tested negative for COVID. -19. They tested positive for adenovirus, a common family of at least 50 different viruses, including the common cold, which typically cause respiratory symptoms but can also cause intestinal problems. Seven of the nine pediatric patients suffered from vomiting or diarrhea before admission, and five of the nine tested positive for adenovirus 41, one of the strains known to affect the gut. None of the children were immunocompromised, none had any other known illnesses, and all were from different parts of the state, ruling out the idea of any local infection.
In three cases, the hepatitis got so bad that the children suffered liver failure. Two children had to undergo a liver transplant. Since then, all nine children have recovered or are on the mend, but the cause of their illness remains unknown.
Alabama is not alone. In April 2022, the World Health Organization (WHO) reported that at least 169 equally mysterious cases of hepatitis emerged in nine countries in Europe as well as Israel, in children aged one month. at 16 years old. So far, worldwide, one death has been reported and 17 children have required liver transplants. At least 74 of the children tested positive for adenovirus and 18 were diagnosed with type 41.
Read more: COVID-19 risks for children under 5 right now: What parents need to know
Cases of pediatric hepatitis have been linked to adenovirus 41 in children in the past, according to the WHO, but only in those who were immunocompromised, which was not the case for any of the children in the global sample group. . After the WHO released its report in late April, Wisconsin, North Carolina and Illinois also reported nine additional cases, with one death in Wisconsin and a liver transplant in Illinois. (These cases were also not mentioned in the recent CDC report.)
What causes the epidemic?
Researchers say active COVID-19 infection is an unlikely link but requires further investigation. Of the 169 children assessed by the WHO as of April 21, only 20 tested positive for SARS-CoV-2 – and 19 of them also had adenovirus. “And we can exclude any type of relationship with the [COVID-19] vaccine,” says Dr. Markus Buchfellner, a pediatric infectious disease physician at the University of Alabama at Birmingham and co-author of the CDC report. Of the nine Alabama patients, seven were not eligible for injections and the two eligible had not yet received any doses.
Six of the Alabama patients tested positive for Epstein-Barr virus (EBV) by PCR test, but were negative for antibodies to the virus, suggesting the infections were not acute, but rather what the CDC report called “low-level reactivation of a previous infection. EBV may be associated with hepatitis A, but it is not the type of hepatitis that the Alabama patients suffered from “These children did not have EBV-related hepatitis,” says Buchfellner.Doctors in Alabama also ruled out autoimmune diseases.
One possible reason for these cases of liver inflammation now being investigated is that lower circulating levels of adenovirus during pandemic shutdowns may have left children’s immune systems unprimed for how to react to the common virus. This, in turn, can allow adenovirus infections to overwhelm children’s immune systems, although exactly why this would lead to liver disease remains unknown. The fact that adenovirus was found in the blood of the nine Alabama children is a powerful piece of evidence, Buchfellner says, because unless there was a very recent infection, the bloodstream clears usually from the virus quite quickly. “In a healthy child, you wouldn’t expect to see the virus in the blood,” he says.
One problem with the adenovirus theory is that liver biopsies were performed on all Alabama children and the virus was not found in any of their liver tissue. That doesn’t mean it was never there; it is possible for the liver to rid itself of the virus after hepatitis has set in. However, its absence in all the biopsies blurs the problem. “That’s the missing piece, in my opinion,” Buchfellner says. “This prevents us from saying with certainty that it was the adenovirus that caused the disease.”
It also still cannot be said with certainty that SARS-CoV-2 played no role in the disease. Acute infection was missing in the Alabama sample group and in most patients worldwide, but that does not rule out the possibility that past infection may play a role. The UK Health Security Agency is investigating the possibility that affected children may have had COVID-19 in the past and this has affected their immune system in some way, making them more susceptible to hepatitis. But the research is preliminary. “My opinion is that there is not enough to know one way or another,” says Buchfellner.
The WHO and the CDC have also not ruled out the emergence of a new, as yet unidentified virus that could be the cause of the epidemic. “All over the world, everyone is working on their adenovirus sequencing,” says Buchfellner. “Over the next few weeks or months, we’ll learn a lot more about that.”
In the meantime, parents should be alert for symptoms of hepatitis, including nausea, vomiting, stomach pain, dark urine, yellowing of the skin or eyes, fever, and fatigue. The cause of the new clusters may not yet be known, but the course of action – seek immediate medical attention if signs of illness appear – is clear.
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