T-Cell Immune Responses in Newborns and Long-Term Sequelae in Congenital Cytomegalovirus Infection (CYTRIC Study)

Abstract

Objective: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae.

Study design: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8⁺ and CD4⁺ T lymphocytes (CMV-IFN-γ-CD8⁺/CD4⁺) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up.

Results: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8⁺ or CD4⁺ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study.

Conclusions: CMV-specific IFN-γ-CD4⁺ and CD8⁺ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.

Keywords: CMV; INF-γ production; T-cell immune response; congenital CMV; congenital infection; cytomegalovirus; hearing loss; interferon-gamma; lymphocytes; newborn.