Herpesvirus reactivation in COVID-19: clinical evidence, mechanistic insights, and research gaps
4 affiliations
- 1Department of Internal Medicine, Hallym University Medical Center, Chuncheon Sacred Heart Hospital
- 2Department of Microbiology, Konkuk University School of Medicine
- 3Department of Infection and Immunology, Konkuk University School of Medicine
- 4KU Open Innovation Center, Research Institute of Medical Science, Konkuk University School of Medicine
Abstract
Herpesviruses establish lifelong latency and can reactivate when antiviral immune surveillance is compromised. Since the onset of COVID-19 pandemic, reactivation of multiple human herpesviruses has increasingly been documented, particularly in patients with severe or critical illness. Herpesvirus reactivation has been associated with prolonged intensive care unit stays, secondary infections, greater ventilatory support requirements, and increased mortality. This review summarizes the latency and reactivation characteristics of the major human herpesviruses and evaluates the clinical evidence linking their reactivation to SARS-CoV-2 infection. We further propose a multifactorial mechanistic framework involving impaired T-cell and natural killer cell surveillance, defective interferon-mediated immunity, sustained inflammation and cytokine signaling, direct and indirect effects of SARS-CoV-2 proteins, and host transcriptional and epigenetic reprogramming. However, despite accumulating clinical and experimental evidence supporting a biologically plausible association between SARS-CoV-2 infection and herpesvirus reactivation, the precise mechanisms underlying this interplay remain incompletely understood. Longitudinal viral monitoring, physiologically relevant latency models, and mechanistic intervention studies are therefore needed to establish causality and identify patients who may benefit from targeted surveillance or antiviral treatment.
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BibTeX
@article{yoo2026herpesvirus,
title = {{Herpesvirus reactivation in COVID-19: clinical evidence, mechanistic insights, and research gaps}},
author = {Jaeyeong Yoo and Ji Soo Park and Jiyun Kim and Seung-Hyun Lee and Un Yung Choi},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1954424},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954424/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Herpesvirus reactivation in COVID-19: clinical evidence, mechanistic insights, and research gaps
AU - Jaeyeong Yoo
AU - Ji Soo Park
AU - Jiyun Kim
AU - Seung-Hyun Lee
AU - Un Yung Choi
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1954424
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954424/full
AB - Herpesviruses establish lifelong latency and can reactivate when antiviral immune surveillance is compromised. Since the onset of COVID-19 pandemic, reactivation of multiple human herpesviruses has increasingly been documented, particularly in patients with severe or critical illness. Herpesvirus reactivation has been associated with prolonged intensive care unit stays, secondary infections, greater ventilatory support requirements, and increased mortality. This review summarizes the latency and reactivation characteristics of the major human herpesviruses and evaluates the clinical evidence linking their reactivation to SARS-CoV-2 infection. We further propose a multifactorial mechanistic framework involving impaired T-cell and natural killer cell surveillance, defective interferon-mediated immunity, sustained inflammation and cytokine signaling, direct and indirect effects of SARS-CoV-2 proteins, and host transcriptional and epigenetic reprogramming. However, despite accumulating clinical and experimental evidence supporting a biologically plausible association between SARS-CoV-2 infection and herpesvirus reactivation, the precise mechanisms underlying this interplay remain incompletely understood. Longitudinal viral monitoring, physiologically relevant latency models, and mechanistic intervention studies are therefore needed to establish causality and identify patients who may benefit from targeted surveillance or antiviral treatment.
SN - 1664-3224
ER -