Increased Output of Recent Thymic Emigrants Contributes to Reconstitution of T‐Cell Pool During Recovery From COVID‐19
Xiaobo Huang, Suvi T. Jokiranta, Kirsten Nowlan, Ngoc Anh Nguyen, Nelli Heikkilä, Lauriina Tola, Anu Kantele, Pirkka T. Pekkarinen, Johanna Hästbacka, Olli Vapalahti, Santtu Heinonen, Juuso Paajanen, Tomas Strandin, Eliisa KekäläinenABSTRACT
Acute coronavirus disease 2019 (COVID‐19) causes marked T‐cell lymphopenia, with recovery potentially driven by peripheral proliferation or increased thymic output of recent thymic emigrants (RTEs). We examined the relative contribution of these mechanisms by analyzing naïve T‐cell and RTE dynamics in 63 patients sampled at 1–3 timepoints during and after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Overall frequencies of naïve CD4+ and CD8+ T cells remained stable during convalescence. In a female‐biased subcohort with paired samples, CD31+ CD4+ and CD21+ CD8+ RTE‐enriched subset frequencies increased from acute to late convalescence (LC) stage. Across the full cohort, a significant increase was confirmed for CD21+ CD8+ RTE‐enriched subsets. PD‐1 and Ki67 expression did not explain this rise, indicating enhancement of thymic output despite the cohort's high median age. Patients requiring ICU care had lower CD31+ CD4+ RTE‐enriched subset frequencies in LC compared with non‐ICU cases. Regression coefficient modeling identified male sex as a negative predictor of CD31+ CD4+ RTE‐enriched subset frequency, potentially contributing to distinct CD31+ CD4+ and CD21+ CD8+ RTE‐enriched subset kinetics. Together, these findings suggest that de novo thymic output, particularly CD21+ CD8+ RTE‐enriched subset, contributes to T‐cell reconstitution after COVID‐19 and may influence susceptibility to post‐infectious immune dysregulation.