ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1693743
This article is part of the Research TopicViral Pathogenesis and Host Defense: Understanding the Missing Links to Combat DiseaseView all 9 articles
Persistent Lymphocytopenia in Convalescent Patients with COVID-19: Dysregulated B Cell, CD4+ T Cell, and Treg Compartments in 7–12% of Moderate-Severe Cases
Provisionally accepted
- Wenzhou Medical University, Wenzhou, China
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Long COVID heterogeneous clinical manifestations suggest a potential link to immune dysfunction, yet the convalescent-phase recovery of immune-cell subsets remains incompletely understood. This longitudinal cohort study enrolled 279 unvaccinated patients (13 mild, 218 moderate, 48 severe) with confirmed SARS-CoV-2 infection, analyzing peripheral lymphocyte subsets via flow cytometry at admission and 50 days post-symptom onset (DPSO 50). While total T-cell counts normalized in 90–98% of moderate-to-severe cases by DPSO 50, a subgroup exhibited persistent B-cell lymphopenia (<90 cells/μL) in 7.3% of moderate cases (median 77.1 cells/μL, IQR 51.9–83.8) and 12.5% of severe cases (median 54.5 cells/μL, IQR 28.4–79.3). Patients with B-cell deficiency demonstrated concurrent reductions in total T cells, CD4⁺ T cells, and CD4⁺CD25⁺CD127low/FOXP3⁺ regulatory T cells (Tregs). Notably, moderate cases displayed significant positive correlations between CD4⁺ T cell and Treg counts (r = 0.72, p < 0.001), independent of B-cell status, whereas severe cases lacked this relationship, indicating severity-dependent immune dysregulation. These findings reveal that 7.3–12.5% of moderate-to-severe survivors retain immunosuppressive states marked by Band T-cell subset lymphopenia, underscoring distinct recovery trajectories and offering insights into Long COVID pathogenesis to guide therapeutic strategies.
Keywords: COVID-19, convalescent patients, Persistent Lymphocytopenia, B cells, T cells, regulatory T cells
Received: 27 Aug 2025; Accepted: 22 Sep 2025.
Copyright: © 2025 An, Yu, Wang, Hu, Zhang, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ming Li, mingli@wmu.edu.cn
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