SLast fall, doctors at Children’s Hospital of Alabama were grappling with a mystery. From October 2021 to February this year, nine children – the youngest 20 months old and the oldest 5 years 9 months old – were taken to the hospital with related symptoms, all due to cases of acute hepatitis liver disease of unknown cause, also known as hepatitis.
As the US Centers for Disease Control and Prevention (CDC) recent report, all patients tested negative for hepatitis A, B and C viruses, and tested negative for COVID-19. They tested positive for adenovirus, a common family of at least 50 different viruses – including the common cold – that commonly cause respiratory symptoms, but can also cause problems. intestinal problems. Seven of the nine pediatric patients experienced vomiting or diarrhea prior to 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 some sort of localized infection. .
In three cases, the hepatitis developed so badly that the children developed liver failure. Two children required a liver transplant. Since then, all 9 children have recovered or are recovering, but the cause of the disease is still unknown.
Alabama is not alone. In April 2022, the World Health Organization (WHO) report that at least 169 cases of similar mysterious hepatitis have occurred in 9 countries in Europe as well as in Israel, in children between one month and 16 years of age. To date, globally, one death has been reported and 17 children required a liver transplant. At least 74 children have tested positive for adenovirus, and 18 have been diagnosed with type 41.
According to WHO, cases of childhood hepatitis have been linked to adenovirus 41 in children, but only in immunocompromised children, which did not occur in any of the children in the global sample. After the WHO issued its report in late April, Wisconsin, North Carolina and Illinois also report an additional nine cases, with one death in Wisconsin and one liver transplant in Illinois. (These cases were also not mentioned in the recent CDC report.)
What is causing the outbreak?
The researchers say that active infection with COVID-19 is an unlikely link but needs further investigation. Of the 169 children assessed by WHO as of April 21, only 20 have tested positive for SARS-CoV-2 — and 19 of those also have adenovirus. “And we can rule out any kind of connection to [COVID-19] “Dr. Markus Buchfellner, a pediatric infectious disease physician at the University of Alabama at Birmingham and a co-author of the CDC report. Of the nine patients in Alabama, seven were ineligible for the shot and two qualified people who have not received any doses.
Six of the Alabama patients became positive for Epstein-Barr virus (EBV) by PCR testing, but they were negative for antibodies to the virus, suggesting that the infection was not acute, but what the CDC report calls “low-level reactivation of previous infection. “EBV may be related to hepatitis A, but it is not the type of hepatitis that the Alabama patient has. “These children do not have EBV hepatitis,” says Buchfellner. The Alabama doctors also ruled out autoimmune disease.
One possible reason for these hepatitis cases currently being investigated is that lower circulating levels of adenovirus during pandemic lockdowns may leave children’s immune systems unprepared to respond. response to common viruses. That, in turn, could facilitate an adenovirus infection to attack children’s immune systems – although exactly why that leads to liver disease remains unknown. Buchfellner says the fact that adenovirus was found in the blood of all nine Alabama children is strong evidence, because unless there is a recent infection, the blood usually clears itself of the virus relatively quickly. “In a healthy child, we wouldn’t expect to see the virus in the blood,” he said.
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 tissues. That doesn’t mean it’s never there; The liver can clear the virus on its own after the hepatitis stops. However, its absence in all biopsies made this problem more difficult. “That’s the missing part, in my opinion,” Buchfellner said. “That makes it impossible for us to say with certainty that it is the adenovirus that causes the disease.”
Nor can it be said with certainty that SARS-CoV-2 played no role in the disease. Acute infection was absent in the Alabama sample group and in most global patients, but that does not rule out the possibility that past infection may have played a role. UK Health Security Agency is considering the possibility that affected children may have had COVID-19 in the past and that affected their immune systems in some way, making them more susceptible to hepatitis. But the research is only preliminary. “My opinion is that there is not enough to know one way or the other,” Buchfellner said.
The WHO and CDC have also not ruled out the emergence of a new, unidentified virus that could cause the outbreak. “All over the world, people are working on sequencing adenoviruses,” says Buchfellner. “Over the next few weeks to months, we’ll learn a lot more about that.”
In the meantime, parents should be on the lookout symptom hepatitis, including nausea, vomiting, stomach pain, dark urine, yellowing of the skin or eyes, fever, and fatigue. The cause of the new clusters may remain unknown, but the course of action — seeking immediate medical attention if signs of illness appear — is clear.
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