Since last autumn, doctors at the Children’s Hospital of Alabama have been wrestling with a mystery. From October 2021 through February of this year, nine children—the youngest 20 months old and the oldest 5 years and 9 months—were rushed to the hospital with concerning symptoms, all of which turned out to be due to unexplained cases of acute hepatitis, also known as liver inflammation.
The U.S. Centers for Disease Control and Prevention reported that all patients were negative for the hepatitis A and B viruses and they also test negative for COVID-19. They did test positive for adenovirus, a common family of at least 50 different viruses—including the common cold—that typically cause respiratory symptoms, but can also cause intestinal problems. Seven of the nine pediatric patients were suffering 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. All of the nine children tested positive for adenovirus 41, which is a strain that affects the gut. They also came from diverse parts of the state.
In 3 cases the severity of the hepatitis caused liver damage. Two of the children needed liver transplants. The cause of the illness has not been determined.
Alabama isn’t the only one. The World Health Organization (WHO), April 20, 2022 reported that at most 169 similar cases of hepatitis were found in Europe and Israel in children aged one to sixteen years. One death has been recorded worldwide and 17 patients have had to receive liver transplants. Minimum 74 children tested positive for the adenovirus and at least 18 with type 41.
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The WHO states that cases of pediatric liver disease have been reported in connection to Adenovirus 41, although this was only for children who had already experienced an immune response. This is not true of any children from the global sample. In addition to the nine cases reported by North Carolina, Illinois and Wisconsin in April’s WHO report, one additional case was also recorded for Illinois. The other one occurred in Illinois. These cases also weren’t included in the CDC’s recent report.
Why is this happening?
Research suggests that COVID-19 active infection is unlikely, but more investigation will be needed. Of the 169 children assessed by the WHO as of April 21, only 20 tested positive for SARS-CoV-2—and 19 of those also had an adenovirus. “And we can rule out any type of relation to the [COVID-19] vaccine,” says Dr. Markus Buchfellner, a pediatric infectious-disease physician at the University of Alabama at Birmingham and a co-author of the CDC report. 7 of nine Alabama patients weren’t eligible to receive shots. Two were not yet eligible.
Six of the Alabama patients did turn up positive for Epstein-Barr virus (EBV) by PCR testing, but they were negative for antibodies to the virus, suggesting that the infections were not acute, but rather what the CDC report called “low-level reactivation of previous infection.” EBV can be associated with hepatitis A, but that is not the type of hepatitis the Alabama patients had. “These children did not have EBV-related hepatitis,” Buchfellner says. Alabama doctors also excluded autoimmune diseases.
One possible reason for these liver-inflammation cases currently under investigation is that lower circulating levels of adenovirus during pandemic lockdowns may have left children’s immune systems unprimed for how to react to the common virus. That, in turn, may be enabling adenovirus infections to overrun children’s immune systems—though exactly why that would result in liver disease remains unknown. Buchfellner said that the fact that all of nine Alabama children had adenovirus in their blood is strong evidence. Unless there was a recent infection, bloodstreams usually get rid of it quickly. “In a healthy child, we would not expect to see the virus in the blood,” he says.
A problem with the adenovirus theory? Liver biopsies were done on every child in Alabama, but the virus was never found in their livers. That doesn’t mean it was never there; it’s possible for the liver to clear itself of the virus after hepatitis takes hold. Its absence from all biopsies obscures the problem. “That is the missing piece, in my opinion,” says Buchfellner. “That keeps us from saying for certain that it’s the adenovirus that caused the disease.”
It also still can’t 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 of the global patients, but that doesn’t rule out the possibility that a past infection might play a role. UK Health Security Agency has begun investigating the possibility of affected children having had COVID-19 previously, which could have affected their immune systems in some manner. This would make them more vulnerable to developing hepatitis. However, the research is only preliminary. “My opinion is that there is not enough to know one way or the other,” says Buchfellner.
The WHO and CDC are not ruling out the possibility of a new virus causing this outbreak. “Across the world, everyone is working on their sequencing of adenoviruses,” Buchfellner says. “Over the next few weeks to months, we will learn a lot more about that.”
Parents should alert their children to the symptoms of Hepatitis. These include nausea, vomiting and stomach pains, as well as dark urine, fatigue, skin yellowing, yellowing, or swelling. The cause of the new clusters may not yet be known, but the course of action—seeking immediate medical attention if signs of the disease appear—is clear.
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