CMV-RNAemia as new marker of active viral replication in transplant recipients
Giulia Piccirilli, Federica Lanna, Liliana Gabrielli, Vincenzo Motta, Martina Franceschiello, Alessia Cantiani, Matteo Pavoni, Marta Leone, E Borgatti, Dino Gibertoni, Renato Pascale, Maddalena Giannella, Francesca Bonifazi, Tiziana Lazzarotto
Abstract
Currently, the quantification of cytomegalovirus (CMV) DNA in blood samples (CMV-DNAemia) represents the gold standard for identifying active viral replication, preventing CMV-related disease, and monitoring response to drugs targeting CMV-DNA polymerase (1–5). The recent introduction of letermovir (LMV) showed that CMV-DNAemia may not be an accurate marker of active viral replication (6–9). Indeed, by blocking the terminase complex, LMV induces the release of free CMV-DNA fragments (abortive infection), which could lead to potential misinterpretation of molecular testing results (1, 6–9). Additional methods, such as CMV-viremia (shell vial method) and CMV-DNAemia post-DNase (DNase test), could be used to prove active viral replication. CMV viremia detects CMV infectious particles in cell culture, whereas the DNase test exploits the digestion activity of DNase I added to the sample before extraction to differentiate free naked DNA from the genome encapsidated into virions. Both methods, therefore, identify the presence of infectious virions in blood samples. However, the procedures are laborious and not standardized (8). This pilot study evaluates the clinical utility of a new CMV-RNAemia test to identify active viral replication and guide pre-emptive or prophylaxis strategies in transplant settings, especially in patients receiving LMV.