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

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.
Competing Interests: Declaration of Competing Interest DBG received fees from MSD as speaker in educational activities. JSL received fees from Biomerieux as speaker. None of the remaining authors have any conflict of interests to declare. This work was supported by projects PI 16/00807, PI 19/01333, and PI 22/01540, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and co-funded by the European Regional Development Fund. DBG was supported by the Spanish Ministry of Science and Innovation - Instituto de Salud Carlos III and by Fondos FEDER “Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 INT20/00  086 and 2023 INT23/00  039”. The study was approved by the Ethics Committee of Hospital Universitario 12 de Octubre. Paula Rodríguez-Molino was funded by the Spanish Ministry of Science and Innovation-Instituto de Salud Carlos III and Fondos FEDER (Contrato Río Hortega CM21/00  174).
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