SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial

Area of Science:

• Immunotherapy
• Virology
• Clinical Trials

Background:

• Limited therapeutic options exist for severe coronavirus disease 2019 (COVID-19).
• Virus-specific T cells demonstrate safety and efficacy in other contexts.
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) offer a potential treatment avenue.

Purpose of the Study:

• To evaluate the safety and efficacy of CoV-2-STs combined with standard of care (SoC) in severe COVID-19 patients.
• To compare outcomes of CoV-2-ST + SoC versus SoC alone during the Delta variant pandemic.
• To assess the in vivo expansion of CoV-2-STs following treatment.

Main Methods:

• A randomized (2:1), open-label, phase 1/2 trial involving 90 participants with severe COVID-19.
• Participants received either CoV-2-STs + SoC or SoC alone.
• Co-primary endpoints included time to recovery, 30-day recovery rate, and CoV-2-ST expansion; survival at day 60 was a key secondary endpoint.

Main Results:

• The CoV-2-ST + SoC group demonstrated a significantly higher recovery rate (65% vs. 38%, P=0.017) and faster median recovery time (11 days vs. not reached, P=0.052).
• Significant expansion of CoV-2-STs was observed in patients receiving the immunotherapy (P=0.047).
• Treatment with CoV-2-STs + SoC was found to be safe and well-tolerated.

Conclusions:

• Adoptive immunotherapy with off-the-shelf, partially HLA-matched CoV-2-STs is feasible and safe for hospitalized patients with severe COVID-19.
• The combination therapy showed preliminary evidence of clinical benefit, meeting primary efficacy endpoints.
• Larger clinical trials are warranted to confirm these findings and strengthen the evidence for CoV-2-STs in severe COVID-19 management.