Monitoring latent viral reactivation in critically ill patients: a review of immunopathology and emerging diagnostics
- 1Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- 2Department of Critical Care Medicine, Wuyi County First People’s Hospital, Jinhua, Zhejiang, China
Abstract
BackgroundCritical illness, particularly sepsis, is characterized by dynamic immune dysregulation in which inflammation and immunosuppressive features coexist. This state may permit reactivation of latent viruses and provides a potential window into host immune competence. This review evaluates latent viral reactivation as an endogenous immunobiological probe in ICU patients and discusses the emerging role of quantitative molecular monitoring.Mechanisms and clinical relevanceLymphocyte depletion, T-cell exhaustion, monocyte dysfunction, reduced antigen presentation, and stress-mediated viral gene regulation contribute to impaired antiviral immune surveillance. Reactivation of cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpesvirus 6, parvovirus B19, and changes in Torque teno virus load have been described in critically ill patients. Multi-virus co-detection and high viral loads may reflect more profound immune dysregulation, although causality and clinically actionable thresholds remain uncertain.Methodological evolutionConventional qPCR remains widely used for clinical viral-load testing, but interpretation is affected by specimen type, target selection, standardization, and low-copy precision. Droplet digital PCR may support absolute quantification, low-abundance detection, and multiplex longitudinal monitoring, but its performance depends on template input, extraction efficiency, assay design and detection thresholds, and it requires careful validation of dynamic range, inhibition controls, over-range reporting, and clinical thresholds.ConclusionsLatent viral reactivation should be interpreted as a dynamic immune-viral signal rather than a simple positive or negative event. TTV is best positioned as a continuous load-based marker of net immune control, while herpesvirus reactivation may help identify specific patterns of impaired antiviral surveillance. ddPCR offers a promising research platform for quantitative immune-viral phenotyping, but further longitudinal validation is needed before routine ICU implementation.
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BibTeX
@article{wu2026monitoring,
title = {{Monitoring latent viral reactivation in critically ill patients: a review of immunopathology and emerging diagnostics}},
author = {Yinshan Wu and Pingli Chen and Feng Guo},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1852101},
url = {https://doi.org/10.3389/fimmu.2026.1852101},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Monitoring latent viral reactivation in critically ill patients: a review of immunopathology and emerging diagnostics
AU - Yinshan Wu
AU - Pingli Chen
AU - Feng Guo
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1852101
UR - https://doi.org/10.3389/fimmu.2026.1852101
AB - BackgroundCritical illness, particularly sepsis, is characterized by dynamic immune dysregulation in which inflammation and immunosuppressive features coexist. This state may permit reactivation of latent viruses and provides a potential window into host immune competence. This review evaluates latent viral reactivation as an endogenous immunobiological probe in ICU patients and discusses the emerging role of quantitative molecular monitoring.Mechanisms and clinical relevanceLymphocyte depletion, T-cell exhaustion, monocyte dysfunction, reduced antigen presentation, and stress-mediated viral gene regulation contribute to impaired antiviral immune surveillance. Reactivation of cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpesvirus 6, parvovirus B19, and changes in Torque teno virus load have been described in critically ill patients. Multi-virus co-detection and high viral loads may reflect more profound immune dysregulation, although causality and clinically actionable thresholds remain uncertain.Methodological evolutionConventional qPCR remains widely used for clinical viral-load testing, but interpretation is affected by specimen type, target selection, standardization, and low-copy precision. Droplet digital PCR may support absolute quantification, low-abundance detection, and multiplex longitudinal monitoring, but its performance depends on template input, extraction efficiency, assay design and detection thresholds, and it requires careful validation of dynamic range, inhibition controls, over-range reporting, and clinical thresholds.ConclusionsLatent viral reactivation should be interpreted as a dynamic immune-viral signal rather than a simple positive or negative event. TTV is best positioned as a continuous load-based marker of net immune control, while herpesvirus reactivation may help identify specific patterns of impaired antiviral surveillance. ddPCR offers a promising research platform for quantitative immune-viral phenotyping, but further longitudinal validation is needed before routine ICU implementation.
SN - 1664-3224
ER -