Adeno-associated virus 2 infection in children with non-A-E hepatitis

Abstract

Summary paragraphAn outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022.1 Cases aged <16 years have since been identified in 35 countries.2 Here we report a detailed investigation of 9 early cases and 58 control subjects. Using next-generation sequencing and real-time PCR, adeno-associated virus 2 (AAV2), was detected in the plasma of 9/9 and liver of 4/4 patients but in 0/13 sera/plasma of age-matched healthy controls, 0/12 children with adenovirus (HAdV) infection and normal liver function and 0/33 children admitted to hospital with hepatitis of other aetiology. AAV2 typically requires a coinfecting ‘helper’ virus to replicate, usually HAdV or a herpesvirus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) were detected in 6/9 and 3/9 affected cases, including 3/4 and 2/4 liver biopsies, respectively. The class II HLA-DRB1*04:01 allele was identified in 8/9 cases (89%), compared with a background frequency of 15.6% in Scottish blood donors, suggestive of increased susceptibility in affected cases. Acute non-A-E paediatric hepatitis is associated with the presence of AAV2 infection, which could represent a primary pathogen or a useful biomarker of recent HAdV or HHV6B infection. Population and mechanistic studies are required to explore these findings further.

Adeno-associated virus type 2 in children from the United States with acute severe hepatitis

“…The location of the AAV2 reference genome (NC_001401.2) is marked with a red asterisk. shared mutations that were reported in another study from the UK and Scotland 12 . Mutational sites that were identified in 100% of cases with sufficient coverage in both studies are highlighted in boldfaced red text.…”

“…Clusters of mutations were found to be located within hypervariable regions of the capsid VP1 and AAP proteins 21 . Of note, 25 (71.4%) of 35 mutations were shared with those identified in an independent study of severe pediatric hepatitis from the UK 12 , with 12 (34.3%) of 35 mutations found in 100% of recovered AAV2 genomes (with coverage at the variable site) from both studies. or amino acid sequences using the MAFFT algorithm 22 , followed by maximum likelihood based tree construction using IQ-TREE 23 .…”

Paediatric hepatitis is linked to infection with two viruses, studies find

“…Researchers from the MRC-University of Glasgow Centre for Virus Research and the Royal Hospital for Children in Glasgow carried out a detailed investigation of nine cases and 58 control participants from Scotland 1. The control group comprised age matched healthy participants, children with adenovirus but normal liver function, and children admitted to hospital with known causes of hepatitis.…”

Vaccinating children aged under 5 years against covid-19

“…Vaccination helps protect adults against prolonged symptoms such as fatigue and loss of smell, but rates of these longer term symptoms are low in children 20. It will be some time before the long term effects of covid-19 (both direct and indirect) on under 5s are fully understood 21…”

“…20 It will be some time before the long term effects of covid-19 (both direct and indirect) on under 5s are fully understood. 21 The US vaccination policy for under 5s may be driven by a desire to protect wider society from further pandemic impacts. Vaccinating children under 5 could reduce circulation of SARS-CoV-2 in the community and limit the risk of further outbreaks in both healthy people and those vulnerable to severe covid-19 such as pregnant women and older adults.…”