CMV-DNAemia, which measures viral DNA in blood, is currently the standard biomarker used to guide antiviral treatment decisions. However, DNAemia does not always reflect active viral replication, as the DNA can persist without reflecting the true infection. In contrast, CMV RNA in plasma derives only from virions during active replication and rapidly decreases once replication ceases. As a result, CMV-RNAemia provides a more accurate indicator of ongoing, infectious viral activity.

Toward reliable monitoring for treatment success

HCMV infections are managed through two main approaches: in pre-emptive treatment, antivirals are provided when viral DNA replication starts1. The second approach is prophylactic therapy, which prevents viral reactivation through immediate antiviral treatment. In this context, Letermovir is commonly used as it is associated with fewer adverse effects.

After Letermovir treatment, viral DNA is released into the bloodstream, causing elevated CMV-DNAemia that does not necessarily indicate active infection2. This discordance complicates treatment decisions, particularly when clinicians rely on DNA thresholds to initiate or discontinue therapy. Because CMV RNA is a marker of true viral replication, it reliably indicates active CMV infection. Measuring CMV RNA in plasma can help clarify ambiguous DNAemia results and guide timely treatment decisions, thereby reducing unnecessary antiviral use and patient toxicity and lowering treatment costs.

Clinical evidence underscoring the value of RNAemia

Recent clinical studies have strengthened the case for CMV-RNAemia as a biomarker for HCMV monitoring and treatment assessment using RT-qPCR assays such as the CMV RNA ELITe MGB Assay (Bruker Corp).

A peer-reviewed study by Piccirilli et al. (J Clin Microbiol., 2024)3 monitored CMV RNAemia in transplant patients receiving Letermovir prophylaxis treatment. CMV RNA and DNA exhibited distinct temporal patterns, peaking simultaneously during active viral replication. In contrast, CMV RNA levels declined earlier than CMV DNA, indicating a treatment response.

Consistent findings were reported in a study by Giardina et al. (J Med Virol., 2025)4, who demonstrated that CMV RNA was associated with packaged virions and serves as a marker of active viral infection. RNAemia and DNAemia are present in clinically significant episodes, and RNAemia cleared approximately 10 days earlier than DNAemia during treatment. RNAemia was detectable in drug-resistant infections, but absent in some cases of high-level DNAemia, suggesting that the detected DNA may reflect non‑active viral replication.

Another study by Nicastro et al., (J. Med. Virol., 2025)5 highlighted the significance of CMV RNAemia in identifying active infection in pediatric cases and demonstrating its correlation with the need for targeted antiviral therapy.

The CMV RNA ELITe MGB® Kit – exclusively from ELITechGroup (a Bruker company)

ELITechGroup pioneered the development of an IVDR-compliant RT-qPCR-based assay for measuring CMV RNAemia in Plasma. The CMV RNA ELITe MGB® Kit targets UL21.5 mRNA, a late transcript incorporated in virions. The assay runs on the fully automated, sample-to-result ELITe InGenius® and ELITe BeGenius® platforms, which integrate nucleic acid extraction, amplification, and result interpretation into a single streamlined workflow. Its high analytical sensitivity enables the detection of CMV RNAemia even at low viral levels. The platforms also allow simultaneous testing of additional parameters, such as HCMV DNA from blood using the CMV ELITe MGB® Kit, providing a comprehensive and efficient solution for complex patient monitoring.

The future of HCMV management

Management of HCMV infection in transplant recipients requires precise and clinically meaningful monitoring. Emerging evidence supports CMV RNAemia as a valuable addition to current strategies. In 2025, international CMV guidelines cited CMV RNAemia as a new biomarker for assessing active viral replication during antiviral therapy6. CMV RNA measurement enables laboratories to deliver clinically meaningful data that supports confident therapeutic decisions and optimises costs through automated workflows.

References

  1. Razonable RR, et al. Cytomegalovirus in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13512.
  2. Cassaniti I, et al. Positive HCMV DNAemia in stem cell recipients undergoing letermovir prophylaxis is expression of abortive infection. Am J Transplant. 2021;21(4):1622–1628.
  3. Piccirilli G, et al. CMV RNAemia as a new marker of active viral replication in transplant recipients. J Clin Microbiol. 2024;27:e0163023.
  4. Giardina F, et al. Human cytomegalovirus virion-associated mRNA as a marker of productive infection in immunocompromised patients. J Med Virol. 2025;97(5):e70378.
  5. Nicastro E, et al. Cytomegalovirus RNA accurately identifies clinically significant infection needing preemptive therapy in liver-transplanted children: A proof-of-concept study. J Med Virol. 2025;97(8):e70521.
  6. Kotton CN, et al.; The Transplantation Society International CMV Consensus Group. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025;109(4):765–792