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New research has provided answers to a mystery involving an outbreak of severe hepatitis in children last year.
A total of about 1,000 cases emerged around the world in spring 2022, after the easing of COVID-19 lockdowns.
Children in about 35 countries, including the United States, experienced severe hepatitis that caused 50 kids to need liver transplants and 22 children to die, according to the study led by researchers at the University of California, San Francisco (UCSF).
The researchers linked the disease to co-infections from multiple common viruses, in particular a strain of adeno-associated virus type 2 (AAV2).
While these AAVs are not known to cause hepatitis on their own, they can with “helper” viruses, such as adenoviruses that cause colds and flu, the study authors explained.
Children who had returned to school were more susceptible to these severe infections.
For a small subset of these children, getting more than one infection at the same time may have made them more vulnerable to severe hepatitis, the investigators found.
“We were surprised by the fact that the infections we detected in these children were caused not by an unusual, emerging virus, but by common childhood viral pathogens,” said senior study author Dr. Charles Chiu, director of the UCSF Clinical Microbiology Laboratory.
“That's what led us to speculate that the timing of the outbreak was probably related to the really unusual situations we were going through with COVID 19-related school and daycare closures and social restrictions,” Chiu said in a university news release. “It may have been an unintended consequence of what we have experienced during the last two to three years of the pandemic.”
By August 2022, there were 358 cases being investigated in the United States and clusters of cases in 34 other countries.
The researchers studied this using polymerase chain reaction (PCR) testing, along with metagenomic sequencing and a molecular testing method. They examined plasma, whole blood, nasal swab and stool samples from 16 pediatric cases in Alabama, California, Florida, Illinois, North Carolina and South Dakota from Oct. 1, 2021, to May 22, 2022.
The researchers compared these specimens with 113 "control" samples.
AAV2 was detected in 93% of the cases and human adenoviruses were found in all the cases. A specific type of adenovirus linked to gastroenteritis was found in 11 cases. Additional co-infections with viruses including Epstein-Barr, herpes and enterovirus were found in about 86% of cases.
The findings mirrored the results of two concurrent studies conducted in the United Kingdom, Chiu said. These identified the same AAV2 strain.
All three studies identified co-infections from multiple viruses. About 75% of the children in the U.S. study had three or four viral infections.
AAVs are not considered pathogenic on their own. A direct causal link with the severe acute hepatitis has yet to be established.
The study authors noted that children may be especially vulnerable to more severe hepatitis triggered by co-infections.
While infections from adeno-associated viruses can occur at any age, the peak is typically between ages 1 and 5 years. The median age of the affected children in the study was 3 years old.
The findings were published March 30 in the journal Nature.
SOURCE: University of California, San Francisco, news release, March 30, 2023
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