10.1111/(ISSN)1365-2141 BJH British Journal of Haematology Br J Haematol 0007-1048 1365-2141 10.1111/bjh.17790 BJH17790 Short Report Short Report Epstein–Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV Venturini Cristina https://orcid.org/0000-0002-4769-7912 1 Houldcroft Charlotte J. https://orcid.org/0000-0002-1833-5285 2 Lazareva Arina https://orcid.org/0000-0002-8902-9146 3 Wegner Fanny https://orcid.org/0000-0003-4348-5872 4 5 Morfopoulou Sofia https://orcid.org/0000-0001-8181-4548 1 Amrolia Persis J. https://orcid.org/0000-0003-0480-3911 3 Golwala Zainab https://orcid.org/0000-0002-8465-5746 6 Rao Anupama https://orcid.org/0000-0001-7959-2229 6 Marks Stephen D. https://orcid.org/0000-0001-9850-8352 7 8 Simmonds Jacob https://orcid.org/0000-0002-1394-4559 6 Yoshikawa Tetsushi https://orcid.org/0000-0002-2847-7682 9 Farrell Paul J. https://orcid.org/0000-0002-6754-9351 10 Cohen Jeffrey I. 11 Worth Austen J. https://orcid.org/0000-0001-6803-7385 12 Breuer Judith https://orcid.org/0000-0001-8246-0534 j.breuer@ucl.ac.uk * 1 6 Institute of Child Health University College London London UK Department of Medicine University of Cambridge Cambridge UK Bone Marrow Transplantation Department Great Ormond Street Hospital for Children NHS Foundation Trust London UK Applied Microbiology Research Department of Biomedicine University of Basel Switzerland Clinical Bacteriology and Mycology University Hospital Basel Basel Switzerland Great Ormond Street Hospital for Children NHS Foundation Trust UK Department of Paediatric Nephrology Great Ormond Street Hospital for Children NHS Foundation Trust UK NIHR Great Ormond Street Hospital Biomedical Research Centre University College London Great Ormond Street Institute of Child Health London UK Department of Pediatrics Fujita Health University School of Medicine Toyoake Japan Section of Virology Department of Infectious Disease Imperial College Faculty of Medicine London UK Laboratory of Infectious Disease National Institute of Allergy and Infectious Diseases Bethesda MD USA Department of Immunology Great Ormond Street Hospital for Children NHS Foundation Trust London UK Correspondence: Judith Breuer, Institute Child Health, University College London, 30 Guilford St., Holborn, London WC1N 1EH, UK. E‐mail: j.breuer@ucl.ac.uk 24 08 2021 04 06 2021 08 08 2021 Copyright © 2021 John Wiley & Sons Ltd © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. 2021 © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Summary

Chronic active Epstein–Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment.

 Epstein–Barr virus chronic active EBV defective viral genome NIHR Imperial Biomedical Research Centre http://dx.doi.org/10.13039/501100013342 Wellcome Trust 204870/Z/16/Z 206478/Z/17/Z MRC MR/S022597/1 NIHR UCL UCLH BRC National Institute of Allergy and Infectious Diseases http://dx.doi.org/10.13039/100000060