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Severe hepatitis outbreak linked to common viruses

A recent study led by the University of California, San Francisco (UCSF) has shed new light on the causes of a peculiar outbreak of acute severe hepatitis that surfaced in otherwise healthy children after Covid-19 lockdowns eased in the United States and 34 other countries in the spring of 2022. With around 1,000 cases reported so far, 50 children have needed liver transplants and at least 22 have died, making this mysterious outbreak highly alarming to healthcare professionals.

The scientists found that the disease was linked to co-infections from multiple common viruses, especially a strain of adeno-associated virus type 2 (AAV2), which do not usually cause hepatitis on its own, but require “helper” viruses – such as adenoviruses causing colds and flus – to replicate in the liver. When children returned to school, they became more vulnerable to infections with these common pathogens, and for a small group of these children, getting more than one infection at the same time made them more susceptible to severe hepatitis.

“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 study senior author Charles Chiu, a professor of Medicine and Clinical Microbiology at UCSF.

“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. It may have been an unintended consequence of what we have experienced during the last two-to-three years of the pandemic.”

The researchers used polymerase chain reaction (PCR) along with various metagenomic sequencing and molecular-testing methods to examine plasma, whole blood, nasal swabs, and stool samples from 16 pediatric cases in six U.S. states, and compared them with 113 control samples. The analyses detected AAV2 in 93 percent of the cases, and human adenoviruses (HAdVs) in all the cases, with additional co-infections with Epstein-Barr, herpes, and enterovirus discovered in 85.7 percent of cases.

Since AAVs are not considered pathogenic on their own, more research is needed to establish a direct causal link with the severe acute hepatitis. However, the findings suggest that co-infections may trigger more severe hepatitis, especially in vulnerable young children whose immune systems lacked their usual “training” through frequent exposure to pathogens due to lockdowns.

Although the clusters of acute severe hepatitis in children have recently declined, frequent handwashing and staying home when sick are still advised to protect children from this developing this frequently debilitating disease.

The study is published in the journal Nature.

By Andrei Ionescu, Staff Writer

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