Acute COVID-19 causes marked T-cell lymphopenia, and how the pool recovers is unclear. Studying 63 patients across acute and convalescent phases, we found that naïve T-cell frequencies stayed stable, whereas recent thymic emigrant (RTE)-enriched subsets rose during recovery. Because this increase was independent of proliferation, it points to renewed thymic output driving T-cell reconstitution, even in a cohort with a mean age of 55 years.
ABSTRACT
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.