Pediatric Hepatitis Outbreak Linked To Childhood Virus

With the easing of COVID-19 lockdowns in the US and 34 other countries in the spring of 2022, scientists are now one step closer to understanding the causes of a puzzling rash of cases of acute severe hepatitis that started to show in otherwise healthy children.
Pediatric hepatitis is uncommon, so when outbreaks of severe unexplained hepatitis began, physicians became concerned. Approximately 1,000 instances have been reported to date; 50 of these kids required liver transplants, and at least 22 of them have passed away.

Researchers in the study, which was published on March 30 in Nature, connected the illness to concomitant infections with several prevalent viruses, particularly a strain of adeno-associated virus type 2. (AAV2). Hepatitis is not typically brought on by AAVs on their own. To reproduce in the liver, “helper” viruses are required, such as the adenoviruses that cause colds and flu.

Children were more vulnerable to infections from these prevalent pathogens once they started going back to school. According to the research, a small subset of these kids may have been more susceptible to developing severe hepatitis if they had multiple infections at once.

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 Charles Chiu, MD, Ph.D., professor of laboratory medicine and medicine in the Division of Infectious Diseases, director of the UCSF Clinical Microbiology Laboratory, and senior author of the paper.

“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. “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, clusters of pediatric hepatitis cases were reported in 35 countries, including the U. S., where 358 cases were under investigation. The Centers for Disease Control and Prevention (CDC) launched an investigation into the causes.

Researchers analyzed plasma, whole blood, nasal swab, and stool samples from 16 pediatric cases in six states—Alabama, California, Florida, Illinois, North Carolina, and South Dakota—between October 1, 2021, and May 22, 2022—using polymerase chain reaction (PCR), as well as various metagenomic sequencing and molecular-testing techniques. 113 control samples were matched to the specimens.

Human adenoviruses (HAdVs) were found in every case when the 14 blood samples were genotyped. An adenovirus specifically linked to gastroenteritis (HAdV-41) was discovered in 11 cases. Adeno-associated virus 2 (AAV2) was identified in 93% of the cases. In 85.7% of instances, Epstein-Barr, herpes, and enterovirus co-infections were also discovered.

Chiu pointed out that the outcomes were consistent with those of two parallel studies carried out in the UK that also found the same AAV2 strain. Infections with multiple viruses were found in all three studies, and 75% of the kids in the American research had three or more viral infections.

A direct causal relationship between AAVs and severe acute hepatitis has not yet been demonstrated because they are not thought to be pathogenic on their own. The research does point out that children may be particularly susceptible to more serious hepatitis brought on by concomitant infections. Although adeno-associated virus infections can happen at any age, the peak is usually between 1 and 5 years old, and the affected children in the research had a median age of 3 years.

Cases of pediatric hepatitis have lately decreased, but according to Chiu, the best defense against this unlikely outcome is hand washing frequently and remaining in when sick.

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