ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1582949
Temporal TCR dynamics and epitope diversity mark recovery in severe COVID-19 Patients
Provisionally accepted
- 1CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India
- 2Academy of Scientific and Innovative Research (AcSIR), New Delhi, National Capital Territory of Delhi, India
- 3Indian Institute of Science Education and Research Kolkata, Kolkata, West Bengal, India
- 4Ashoka University, Sonepat, Haryana, India
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Severe COVID-19 is marked by immune dysregulation, with T cells playing a key role in disease progression and recovery. However, the temporal dynamics of T cell receptor (TCR) repertoires in severe cases remain unclear. To address this, we tracked ICU-admitted severe COVID-19 patients across three time points. By T3, a 2.3-fold expansion in TCR clonotypes and increased TCR-β (TRB) chain usage indicated a robust polyclonal response essential for viral clearance. Simultaneously, reduced TCR-γ (TRG) chain prevalence and lower pro-inflammatory cytokines (IL-1β, IL-6) marked a shift from acute inflammation to immune regulation. Altered CDR3 motifs and preferential TRBV segment usage highlighted TCR adaptation to SARS-CoV-2 epitopes, while diversification targeted latent pathogens like cytomegalovirus and Plasmodium, suggests predicted cross-reactivity or memory T cell recruitment, reflecting enhanced immune surveillance. Integrating TCR repertoire data with cytokine profiles reveals a coordinated immune shift from dysfunction to recovery, underscoring pathways critical for resolving severe infections and advancing our understanding of immune resilience in viral diseases.
Keywords: COVID-19, ICU-admitted patients, TCR dynamics, TCR clonotypes, Adaptive regulation
Received: 26 Feb 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Pandey, Khare, Yadav, Halder, Ray and Ganguly. 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: Rajesh Pandey, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India
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