{"doi":"10.1093/cid/ciab371","title":"Vaccinated and Convalescent Donor–Derived Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients","abstract":"BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for 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 polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an \"off-the shelf\" T-cell immunotherapy for high-risk patients.","journal":"Clinical Infectious Diseases","year":2021,"id":176314,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9419,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":718812,"name":"D. Chasiotis","orcid":null,"position":1,"is_corresponding":false},{"id":718381,"name":"Kiriakos Koukoulias","orcid":"0000-0002-3530-048X","position":2,"is_corresponding":false},{"id":309008,"name":"Aphrodite Georgakopoulou","orcid":"0000-0003-1541-7549","position":3,"is_corresponding":false},{"id":718382,"name":"Anastasia Iatrou","orcid":"0000-0002-8995-4454","position":4,"is_corresponding":false},{"id":440430,"name":"Eleni Gavriilaki","orcid":"0000-0002-8883-8208","position":5,"is_corresponding":false},{"id":718813,"name":"Chrysavgi Giannaki","orcid":null,"position":6,"is_corresponding":false},{"id":718814,"name":"Militsa Bitzani","orcid":null,"position":7,"is_corresponding":false},{"id":718815,"name":"E Geka","orcid":null,"position":8,"is_corresponding":false},{"id":718816,"name":"Polychronis Tasioudis","orcid":null,"position":9,"is_corresponding":false},{"id":718817,"name":"Diamantis Chloros","orcid":null,"position":10,"is_corresponding":false},{"id":718383,"name":"Asimina Fylaktou","orcid":"0000-0001-5973-3549","position":11,"is_corresponding":false},{"id":718818,"name":"Ioannis Kioumis","orcid":null,"position":12,"is_corresponding":false},{"id":718384,"name":"Maria Triantafyllidou","orcid":"0000-0002-2239-2696","position":13,"is_corresponding":false},{"id":718819,"name":"Sotiria Dimou‐Besikli","orcid":null,"position":14,"is_corresponding":false},{"id":718385,"name":"Georgios Karavalakis","orcid":"0000-0001-5011-8371","position":15,"is_corresponding":false},{"id":718386,"name":"Afroditi Boutou","orcid":"0000-0001-7366-2038","position":16,"is_corresponding":false},{"id":718820,"name":"Eleni Siotou","orcid":null,"position":17,"is_corresponding":false},{"id":440432,"name":"Αchilles Anagnostopoulos","orcid":"0000-0003-4384-9031","position":18,"is_corresponding":false},{"id":718387,"name":"Αναστασία Παπαδοπούλου","orcid":"0000-0001-5385-8738","position":19,"is_corresponding":false},{"id":309009,"name":"Evangelia Yannaki","orcid":"0000-0002-9849-1279","position":20,"is_corresponding":false},{"id":718811,"name":"Penelope‐Georgia Papayanni","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"33905481","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}