Third-Party Cytotoxic T Lymphocytes for High-Risk Patients with Covid-19

Abstract Treatment with off-the-shelf cellular therapy may provide direct and rapid treatment for COVID-19, overcoming the delayed adaptive immune responses associated with poor outcomes in high-risk patients. Thirty ambulatory patients with COVID-19 were enrolled on a phase I trial to assess the safety of 3rd party, COVID-19-specific cytotoxic T lymphocytes (CTLs). Twelve “Interventional” patients matching the HLA-A*02:01 restriction of the CTLs received a single infusion of one of four escalating doses of a product containing 68.5% COVID-19-specific CD8+ CTLs/total cells. Eighteen “Observational” patients lacking HLA-A*02:01 served as comparisons. No dose-limiting toxicities were observed. Nasal swab PCR data showed ≥ 88% viral elimination in 92% of patients in 4 days and the CTLs remained detectable at 6 months. Interventional patients consistently reported symptomatic improvement 2-3 days after infusion, whereas improvement was more variable in Observational patients. Our study shows that COVID-19-specific CTLs are a potentially useful cellular therapy for COVID-19.