Signatures of AAV-2 immunity are enriched in children with severe acute hepatitis of unknown etiology

Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children’s of Alabama and compared their antibody responses to 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and detailed adeno-associated virus 2 (AAV-2) peptide responses that were conserved in 7 of 9 cases but rarely observed in pediatric and adult control. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.