Adenovirus infection after cellular therapy: diagnostic and therapeutic challenges

To review recent advances in the epidemiology, diagnosis, and management of human adenovirus (HAdV) infection following haematopoietic cell transplantation (HCT) and other cellular therapies, with emphasis on risk stratification, molecular surveillance, and emerging therapies.

Recent studies have improved understanding of the interplay between viral burden, immune reconstitution, and progression to invasive HAdV disease following HCT. International consensus definitions of HAdV infection and disease have recently been proposed and may improve consistency in the reporting of clinical and research outcomes. Increasing evidence supports the gastrointestinal tract as a reservoir for viral persistence, with rising stool viral loads often preceding invasive infection. Intravenous brincidofovir has emerged as a promising alternative to cidofovir, demonstrating preliminary antiviral activity without the nephrotoxicity associated with cidofovir or the gastrointestinal toxicity observed with oral brincidofovir. HAdV-specific cytotoxic T-lymphocyte therapies have also shown encouraging efficacy in refractory infection.

HAdV remains an important cause of morbidity and mortality following HCT, particularly in patients with impaired T-cell immunity. Key challenges include optimal surveillance strategies, treatment thresholds, and management of high-risk patients. Advances in molecular diagnostics, standardized disease definitions, brincidofovir, and virus-specific T-cell therapies may facilitate higher quality clinical research and support more standardized, evidence-based approaches to HAdV management.