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. 2025 Aug:277:110510.
doi: 10.1016/j.clim.2025.110510. Epub 2025 Apr 30.

Incidence and risk factors for CMV and EBV infection in infants with low T-cell receptor excision circles on newborn screen

Megan E Day-Lewis  1 , Laura Berbert  2 , Michele DeGrazia  3 , Christina Yee  4 , Ari J Fried  4 , Alan A Nguyen  4 , Jaime E Hale  5 , Anne Counihan  5 , Anne Marie Comeau  6 , Elsa R Treffeisen  4 , Mary Poyner Reed  7 , Craig D Platt  4 , Janet Chou  4
Affiliations

Incidence and risk factors for CMV and EBV infection in infants with low T-cell receptor excision circles on newborn screen

Megan E Day-Lewis et al. Clin Immunol. 2025 Aug.

Abstract

Background: Newborn screening for severe combined immunodeficiency (SCID) using T cell receptor excision circles (TRECs) identifies patients with other causes of lymphopenia. The risk of opportunistic infection in patients with non-SCID lymphopenia is poorly understood. We aim to describe incidence and risk factors associated with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in patients with low TRECs.

Methods: This retrospective study analyzed 289 patients with ≥1 abnormal TREC result.

Results: Nineteen patients had CMV or EBV detected by PCR. Most had resolution of infection (n = 13). Two have chronic viremia, and four expired due to disseminated CMV. Risk factors included undetectable TRECs, consanguinity, family history, low NK, naïve CD4, naïve CD8 cells, and phytohemagglutinin.

Conclusion: Infection with CMV and EBV in patients with low TRECs is rare, however some may benefit from preventative measures. Consideration of risk factors may aid in decision-making and improve outcomes.

Keywords: Cytomegalovirus; Epstein-Barr virus; Lymphopenia; Newborn screening; Severe combined immunodeficiency; T cell receptor excision circle.

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Conflict of interest statement

Declaration of competing interest The authors declare no potential financial conflicts of interest related to this work.

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