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<p>Advanced age, comorbidities, and immunocompromised states remain major risk factors for severe or persistent COVID-19 despite vaccination and antivirals, underscoring the need for innovative treatments such as adoptive T-cell therapy (ATT). In this prospective single-center study, we evaluated the safety, feasibility, and efficacy of two ATT approaches in immunocompromised patients with high-risk or persistent SARS-CoV-2 infection: interferon-γ cytokine capture system virus-specific T cells (IFN-γ CCS VST, n = 12; median age 59) and CD45RA + T-cell depleted donor lymphocyte infusion (CD45RA<sup>+</sup> TCD DLI, <i>n</i> = 11; median age 46). Most patients (73.9%) had undergone prior hematopoietic stem cell transplantation (HSCT). Both treatments were safe, with no adverse events observed. One-year overall survival (OS) did not differ significantly between groups (<i>p</i> = 0.8907 overall; <i>p</i> = 0.5907 in HSCT recipients). However, CD45RA<sup>+</sup> TCD DLI showed a trend toward improved 1-year COVID-19–free survival (<i>p</i> = 0.058) and significantly better survival among HSCT recipients (<i>p</i> = 0.0362). Viral clearance was achieved in most patients (90.9% vs. 83.3%). Immunomonitoring revealed distinct immune dynamics: between weeks 5–8, IFN-γ CCS VST promoted naïve T-cell expansion with broad cytokine elevation, while CD45RA<sup>+</sup> TCD DLI expanded memory T cells with a more restricted cytokine profile. IFN-γ CCS VST also elicited stronger in vivo expansion of SARS-CoV-2–specific CD4 + and CD8 + T cells. In summary, both ATT approaches are safe and effective in immunocompromised patients with persistent COVID-19. CD45RA<sup>+</sup> TCD DLI, which can be generated from convalescent donors as an off-the-shelf product, may provide a practical strategy for pandemic preparedness and treatment of vulnerable patients with immune senescence.</p> Graphical Abstract <p></p>

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Adoptive T-cell therapies for persistent COVID-19 in immunocompromised patients: Comparison of IFN-γ virus-specific T-cell therapy and CD45RA+ T-cell depleted donor lymphocyte infusion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月12日

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  • László Gopcsa,
  • Borisz Rabán Petrik,
  • Bálint Gergely Szabó,
  • Marienn Réti,
  • Hajnalka Andrikovics,
  • Ilona Bobek,
  • Gabriella Bekő,
  • Judit Bogyó,
  • Andrea Ceglédi,
  • Katalin Dobos,
  • Laura Giba-Kiss,
  • Orsolya Kis,
  • Botond Lakatos,
  • Dóra Mathiász,
  • Nóra Meggyesi,
  • Gottfried Miskolczi,
  • Noémi Németh,
  • János Sinkó,
  • Anikó Szilvási,
  • János Szlávik,
  • Szabolcs Tasnády,
  • Zsuzsanna Várnai,
  • Péter Reményi,
  • István Vályi-Nagy

摘要

Advanced age, comorbidities, and immunocompromised states remain major risk factors for severe or persistent COVID-19 despite vaccination and antivirals, underscoring the need for innovative treatments such as adoptive T-cell therapy (ATT). In this prospective single-center study, we evaluated the safety, feasibility, and efficacy of two ATT approaches in immunocompromised patients with high-risk or persistent SARS-CoV-2 infection: interferon-γ cytokine capture system virus-specific T cells (IFN-γ CCS VST, n = 12; median age 59) and CD45RA + T-cell depleted donor lymphocyte infusion (CD45RA+ TCD DLI, n = 11; median age 46). Most patients (73.9%) had undergone prior hematopoietic stem cell transplantation (HSCT). Both treatments were safe, with no adverse events observed. One-year overall survival (OS) did not differ significantly between groups (p = 0.8907 overall; p = 0.5907 in HSCT recipients). However, CD45RA+ TCD DLI showed a trend toward improved 1-year COVID-19–free survival (p = 0.058) and significantly better survival among HSCT recipients (p = 0.0362). Viral clearance was achieved in most patients (90.9% vs. 83.3%). Immunomonitoring revealed distinct immune dynamics: between weeks 5–8, IFN-γ CCS VST promoted naïve T-cell expansion with broad cytokine elevation, while CD45RA+ TCD DLI expanded memory T cells with a more restricted cytokine profile. IFN-γ CCS VST also elicited stronger in vivo expansion of SARS-CoV-2–specific CD4 + and CD8 + T cells. In summary, both ATT approaches are safe and effective in immunocompromised patients with persistent COVID-19. CD45RA+ TCD DLI, which can be generated from convalescent donors as an off-the-shelf product, may provide a practical strategy for pandemic preparedness and treatment of vulnerable patients with immune senescence.

Graphical Abstract