PMID- 37460756
OWN - NLM
STAT- MEDLINE
DCOM- 20230817
LR  - 20230926
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 29
IP  - 8
DP  - 2023 Aug
TI  - SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 
      trial.
PG  - 2019-2029
LID - 10.1038/s41591-023-02480-8 [doi]
AB  - Despite advances, few therapeutics have shown efficacy in severe coronavirus 
      disease 2019 (COVID-19). In a different context, virus-specific T cells have 
      proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 
      trial to evaluate the safety and efficacy of off-the-shelf, partially human 
      leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute 
      respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in 
      combination with standard of care (SoC) in patients with severe COVID-19 compared 
      to SoC during Delta variant predominance. After a dose-escalated phase 1 safety 
      study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC 
      only (n = 30). The co-primary objectives of the study were the composite of time 
      to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in 
      patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was 
      survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study 
      met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% 
      versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, 
      respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, 
      P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion 
      compared to SomicronC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized 
      patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible 
      and safe. Larger trials are needed to strengthen the preliminary evidence of 
      clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Papadopoulou, Anastasia
AU  - Papadopoulou A
AUID- ORCID: 0000-0001-5385-8738
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Karavalakis, George
AU  - Karavalakis G
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Papadopoulou, Efthymia
AU  - Papadopoulou E
AUID- ORCID: 0000-0002-2415-0842
AD  - Department of Respiratory Medicine, George Papanikolaou Hospital, Thessaloniki, 
      Greece.
FAU - Xochelli, Aliki
AU  - Xochelli A
AD  - Department of Immunology, National Peripheral Histocompatibility Center, 
      Hippokration General Hospital, Thessaloniki, Greece.
FAU - Bousiou, Zoi
AU  - Bousiou Z
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Vogiatzoglou, Anastasios
AU  - Vogiatzoglou A
AD  - Department of Respiratory Medicine, George Papanikolaou Hospital, Thessaloniki, 
      Greece.
FAU - Papayanni, Penelope-Georgia
AU  - Papayanni PG
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
AD  - Department of Genetics, Development and Molecular Biology, School of Biology, 
      Aristotle University of Thessaloniki, Thessaloniki, Greece.
FAU - Georgakopoulou, Aphrodite
AU  - Georgakopoulou A
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
AD  - Department of Genetics, Development and Molecular Biology, School of Biology, 
      Aristotle University of Thessaloniki, Thessaloniki, Greece.
FAU - Giannaki, Maria
AU  - Giannaki M
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Stavridou, Fani
AU  - Stavridou F
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Vallianou, Ioanna
AU  - Vallianou I
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Kammenou, Maria
AU  - Kammenou M
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Varsamoudi, Evangelia
AU  - Varsamoudi E
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Papadimitriou, Vasiliki
AU  - Papadimitriou V
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Giannaki, Chrysavgi
AU  - Giannaki C
AD  - 'A' Intensive Care Unit, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Sileli, Maria
AU  - Sileli M
AD  - 'B' Intensive Care Unit, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Stergiouda, Zoi
AU  - Stergiouda Z
AD  - Department of Anesthesiology, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Stefanou, Garyfallia
AU  - Stefanou G
AD  - ECONCARE LP, Athens, Greece.
FAU - Kourlaba, Georgia
AU  - Kourlaba G
AD  - Department of Nursing, University of Peloponnese, Tripolis, Greece.
FAU - Gounelas, George
AU  - Gounelas G
AD  - ECONCARE LP, Athens, Greece.
FAU - Triantafyllidou, Maria
AU  - Triantafyllidou M
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Siotou, Eleni
AU  - Siotou E
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Karaglani, Antonia
AU  - Karaglani A
AD  - Euromedica Arogi Rehabilitation Center, Thessaloniki, Greece.
FAU - Zotou, Eleni
AU  - Zotou E
AUID- ORCID: 0009-0008-7113-378X
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
AD  - Department of Genetics, Development and Molecular Biology, School of Biology, 
      Aristotle University of Thessaloniki, Thessaloniki, Greece.
FAU - Chatzika, Georgia
AU  - Chatzika G
AD  - Department of Immunology, National Peripheral Histocompatibility Center, 
      Hippokration General Hospital, Thessaloniki, Greece.
FAU - Boukla, Anna
AU  - Boukla A
AD  - Department of Immunology, National Peripheral Histocompatibility Center, 
      Hippokration General Hospital, Thessaloniki, Greece.
FAU - Papalexandri, Apostolia
AU  - Papalexandri A
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Koutra, Maria-Georgia
AU  - Koutra MG
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Apostolou, Dimitra
AU  - Apostolou D
AD  - Department of Respiratory Failure, George Papanikolaou Hospital, Aristotle 
      University of Thessaloniki, Thessaloniki, Greece.
FAU - Pitsiou, Georgia
AU  - Pitsiou G
AD  - Department of Respiratory Failure, George Papanikolaou Hospital, Aristotle 
      University of Thessaloniki, Thessaloniki, Greece.
FAU - Morfesis, Petros
AU  - Morfesis P
AD  - 1st Department of Internal Medicine, AHEPA University Hospital, Aristotle 
      University of Thessaloniki, Thessaloniki, Greece.
FAU - Doumas, Michalis
AU  - Doumas M
AD  - 2nd Propedeutic Department of Internal Medicine, Hippokrateio Hospital, Aristotle 
      University of Thessaloniki, Thessaloniki, Greece.
FAU - Karampatakis, Theodoros
AU  - Karampatakis T
AD  - Department of Microbiology, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Kapravelos, Nikolaos
AU  - Kapravelos N
AD  - 'B' Intensive Care Unit, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Bitzani, Militsa
AU  - Bitzani M
AD  - 'A' Intensive Care Unit, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Theodorakopoulou, Maria
AU  - Theodorakopoulou M
AD  - National and Kapodistrian University of Athens, Evaggelismos General Hospital, 
      Athens, Greece.
FAU - Serasli, Eva
AU  - Serasli E
AD  - Department of Respiratory Medicine, George Papanikolaou Hospital, Thessaloniki, 
      Greece.
FAU - Georgolopoulos, Grigorios
AU  - Georgolopoulos G
AUID- ORCID: 0000-0002-9906-4797
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Sakellari, Ioanna
AU  - Sakellari I
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Fylaktou, Asimina
AU  - Fylaktou A
AD  - Department of Immunology, National Peripheral Histocompatibility Center, 
      Hippokration General Hospital, Thessaloniki, Greece.
FAU - Tryfon, Stavros
AU  - Tryfon S
AUID- ORCID: 0000-0001-5102-0480
AD  - Department of Respiratory Medicine, George Papanikolaou Hospital, Thessaloniki, 
      Greece.
FAU - Anagnostopoulos, Achilles
AU  - Anagnostopoulos A
AUID- ORCID: 0000-0003-4384-9031
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece.
FAU - Yannaki, Evangelia
AU  - Yannaki E
AUID- ORCID: 0000-0002-9849-1279
AD  - Hematopoietic Cell Transplantation Unit, Department of Hematology Gene and Cell 
      Therapy Center, George Papanikolaou Hospital, Thessaloniki, Greece. 
      eyannaki@u.washington.edu.
AD  - Department of Medicine, University of Washington, Seattle, WA, USA. 
      eyannaki@u.washington.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230717
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - SARS-CoV-2 variants
SB  - IM
MH  - Humans
MH  - *COVID-19/therapy
MH  - SARS-CoV-2
MH  - Immunotherapy, Adoptive/adverse effects
MH  - Cell- and Tissue-Based Therapy
MH  - Treatment Outcome
EDAT- 2023/07/18 01:09
MHDA- 2023/08/17 06:42
CRDT- 2023/07/17 23:30
PHST- 2022/11/04 00:00 [received]
PHST- 2023/06/28 00:00 [accepted]
PHST- 2023/08/17 06:42 [medline]
PHST- 2023/07/18 01:09 [pubmed]
PHST- 2023/07/17 23:30 [entrez]
AID - 10.1038/s41591-023-02480-8 [pii]
AID - 10.1038/s41591-023-02480-8 [doi]
PST - ppublish
SO  - Nat Med. 2023 Aug;29(8):2019-2029. doi: 10.1038/s41591-023-02480-8. Epub 2023 Jul 
      17.