SYSTEMATIC REVIEW article
Front. Virol.
Sec. Viral Disease Investigation
Volume 5 - 2025 | doi: 10.3389/fviro.2025.1641157
A Systematic Review of HHV-6 Infections in Recipients of Organ and Tissue Transplantation and Chimeric Antigen Receptor T-Cell (CAR-T) Infusions
Provisionally accepted
- 1University of the Philippines Manila College of Medicine, Manila, Philippines
- 2Mayo Clinic Minnesota, Rochester, United States
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We systematically reviewed published literature to describe the epidemiology and outcomes of HHV-6 syndromes and diseases after solid organ transplantation (SOT), hematopoietic transplantation (HCT), and chimeric antigen receptor t-cell (CAR-T) therapy.METHODS: PUBMED, SCOPUS, EMBASE, and OVID/MEDLINE were reviewed from inception through May 31, 2024 using key words HHV-6 and transplantation or CAR-T. We included abstracts, case reports, cohort and case-control studies among adults, published or translated into English.A total of 136 case reports or series contributed 268 unique cases -225 HCT, 37 SOT, and 6 CAR-T, while 39 cohort studies on HCT (28), SOT (9) and CAR-T (1), and mixed SOT/HCT (1) recipients were included. HHV-6 incidence varied widely from 1-95% among cohort studies in HCT and SOT, but was low in CAR-T recipients (5.6%). Among case reports, the median age was 46 (range 18-73) years, and most were male (159/236, 67.4%). HHV-6 subtyping was performed only in 66 cases, and 46 were variant B. Ten cases were chromosomally integrated (ciHHV-6).Among 268 cases with detailed clinical information, fever was reported only in 89 patients (33.2%). The most common clinical syndrome was neurologic (204/268, 76.1%), followed by viral syndrome (28/268, 10.4%) and disseminated disease (14/268 5.2%). Initial therapy was ganciclovir (87/234, 37.2%) or foscarnet (82/234, 35%). At least a third of patients developed neurologic sequelae (45/151, 29.8%).HHV-6 attributable mortality was 20.6% (22/107).Neurologic disease is the most frequent clinical syndrome of HHV-6 infection. Early recognition of limbic involvement either through the triad of confusion, amnesia, or seizures, or through compatible MRI imaging findings may help with early identification. Diagnosis is secured through molecular methods, although extremely high viral load needs to be interpreted in the context of ciHHV-6.Neurologic sequelae of HHV-6 can be disabling and cause significant morbidity.
Keywords: HHV 6, HHV6-induced post-transplantation acute limbic encephalitis, Solid organ transplant (SOT), hematopoietic (stem cell) transplant (HSCT), viral infection, transplant infections, review - systematic
Received: 04 Jun 2025; Accepted: 09 Jul 2025.
Copyright: © 2025 Abad and Razonable. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cybele Lara Abad, University of the Philippines Manila College of Medicine, Manila, Philippines
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