TY - JOUR
AU - Morfopoulou, Sofia
AU - Buddle, Sarah
AU - Montaguth, Oscar Enrique Torres
AU - Atkinson, Laura
AU - Assuncao, Jose Afonso Guerra
AU - Storey, Nathaniel
AU - Roy, Sunando
AU - Lennon, Alexander
AU - Lee, Jack C. D.
AU - Williams, Rachel
AU - Williams, Charlotte A.
AU - Tutill, Helena
AU - Bayzid, Nadua
AU - Bernal, Luz Marina Martin
AU - Moore, Catherine
AU - Templeton, Kate
AU - Neill, Claire O.
AU - Holden, Matthew T.G.
AU - Gunson, Rory N.
AU - Shepherd, Samantha J.
AU - Shah, Priyen
AU - Cooray, Samantha
AU - Voice, Marie
AU - Steele, Michael
AU - Fink, Colin
AU - Whittaker, Thomas E.
AU - Santilli, Giorgia
AU - Gissen, Paul
AU - Brown, Rachel
AU - Kaufer, Benedikt B.
AU - Reich, Jana
AU - Andreani, Julien
AU - Simmonds, Peter
AU - Alrabiah, Dimah K.
AU - Hereza, Sergi Castellano
AU - DIAMONDS and PERFORM Consortia
AU - Andrade, Catarina
AU - Anderson, Glenn
AU - Kelgeri, Chayarani
AU - Waddington, Simon N.
AU - Diaz, Juan Antinao
AU - Hatcher, James
AU - De, Surjo
AU - Chiozzi, Riccardo Zenezini
AU - Thalassinos, Konstantinos
AU - Jacques, Thomas S.
AU - Talts, Tiina
AU - Hoschler, Katja
AU - Celma, Cristina
AU - Gonzalez, Suam
AU - Gallagher, Eileen
AU - Simmons, Ruth
AU - Watson, Conall
AU - Mandal, Sema
AU - Zambon, Maria
AU - Chand, Meera
AU - Campos, Luis
AU - Martin, Joanne
AU - Thomson, Emma C.
AU - Ushiro-Lumb, Ines
AU - Levin, Michael
AU - Brown, Julianne R.
AU - Breuer, Judith
PY - 2022
DA - July
TI - Genomic investigations of acute hepatitis of unknown aetiology in children
JO - medRxiv
DO - https://doi.org/10.1101/2022.07.28.22277963
AB - Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic  and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver  transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 nontransplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV6B), both of which enable AAV2 lytic replication, were  also found in the five explanted livers and blood from 15/17 and 6/9  respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained  hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.
PB - medRxiv
UR - https://publichealthscotland.scot/id/90980
KW - Coronavirus (COVID-19)
KW - Children, young people and families
ER