Vaccinated and convalescent donor-derived SARS-CoV-2-specific T cells as adoptive immunotherapy for high-risk COVID-19 patients.

摘要: Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies Coronavirus Disease 2019 (COVID-19). Methods We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19 infected individuals (convalescent), asymptomatic PCR-positive subjects, vaccinated individuals, non-ICU hospitalized patients ICU who either recovered were discharged (ICU recovered) or had a prolonged stay and/or died critical). CoV-2-STs generated from all types donors underwent phenotypic functional assessment. Results demonstrate causal relationship between endogenous disease outcome; insufficient circulating CoV-2-STs, identified at high-risk adverse outcome. with similarly non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded both convalescent generating clinical-scale, products activity unmutated virus its B.1.1.7 variant. In contrast, critical patient-originating failed to expand, recapitulating vivo failure CoV-2-specific control infection. PCR+ presented only weak responses whereas their counterparts originating exposed other seasonal coronaviruses subjects kill virus, thus disempowering hypothesis protective cross-immunity. Conclusions Overall, we provide evidence on risk stratification feasibility powerful CoV-2-ST as "off-the shelf" immunotherapy patients.