Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy (RELEASE)

L Herrera(1,2) M Martin-Inaraja(1,2) S Santos(1,2) M Inglés-Ferrándiz(1,2) A Azkarate(1,2) M Burón(1,2) M A Pérez-Vaquero(1,2) M A Vesga(1,2) J L Vicario(3) B Soria(4,5) C Solano(6,7) R de Paz(8) A Marcos(8) C Ferreras(9) A Pérez-Martínez(9,10,11) C Eguizabal(1,2)

1:Research Unit, Basque Center for Blood Transfusion and Human Tissues, Osakidetza, Galdakao, Spain.; 2:Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.; 3:Histocompatibility, Centro de Transfusión de Madrid, Madrid, Spain.; 4:Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Alicante, Spain; 5:Instituto de Investigación Sanitaria Hospital General y Universitario de Alicante (ISABIAL), Alicante, Spain.; 6:Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain; 7:School of Medicine, University of Valencia, Spain.; 8:Hematology Department, University Hospital La Paz, Madrid, Spain.; 9:Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain.; 10:Pediatric Hemato-Oncology Department, University Hospital La Paz, Madrid, Spain.; 11:Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. Unlike T lymphocytes, NK cells are not known for their specific memory population. Nevertheless, studies regarding NK cell population in other viral infections, such as cytomegalovirus, have shown specific memory population of these cells. These NK cells are particularly re-activated when facing viral specific peptides. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Moreover, this “memory” population respond to the presence of SARS-CoV-2 peptides. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210). NK cells from selected donors’ have been isolated, frozen and storage. NK cell arm of RELEASE clinical trial has been initiated in several patients.