Allogeneic 'off-the-shelf' SARS-CoV-2-specific adoptive T-cell therapy for refractory viral infection and end organ disease.

Objectives: Despite the effective roll-out of COVID-19 vaccines, immunocompromised patients have a higher risk of morbidity and mortality following SARS-CoV-2 infection. Allogeneic adoptive T-cell immunotherapy is now established as an effective approach to treat viral diseases in immunocompromised patients. The objective of this study was to assess the safety of allogeneic virus-specific T-cell therapy in patients with COVID-19. Methods: Using a repository of SARS-CoV-2-specific T cells generated from healthy exposed volunteers, we conducted an open-label phase I trial to assess the feasibility and safety of allogeneic SARS-CoV-2-specific T cells in immune-compromised cancer patients with COVID-19. Results: Six participants at risk of severe COVID-19 were enrolled and received SARS-CoV-2-specific T-cell therapy within 4 days of recruitment. The first five participants who received two infusions of allogeneic SARS-CoV-2-specific T-cell therapy experienced no adverse events following treatment. Four of the six participants showed improvement in viral load following treatment and were alive at 12-week follow-up. One participant died 6 days after their second infusion, because of established pulmonary parenchymal damage following prolonged COVID infection. Another, who had underlying lupus nephritis, developed cytokine release syndrome and diffuse alveolar haemorrhage following a single infusion and was withdrawn from the study. They subsequently recovered from this serious adverse event. Conclusion: Allogeneic SARS-CoV-2-specific T-cell therapy provides a platform to rapidly administer T cells to high-risk COVID-19 patients. It was associated with a reduced viral load and increased SARS-CoV-2-specific T-cell responses in the majority of treated patients.