The phase I RELEASE clinical trial to evaluate the safety of NK cells in COVID-19
The severity of COVID 19 symptoms has a direct correlation with lymphopenia, affecting natural killer (NK) cells. SARS-CoV-2 specific "memory" NK cells obtained from convalescent donors can be used as cell immunotherapy. In 2022 a phase I, dose-escalation, single center clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD3<sup>-</sup>/CD56<sup>+</sup> NK cells against moderate/severe cases of COVID-19 (NCT04578210). Six participants with pneumonia and/or lymphopenia were infused. Four patients received a single-dose infusion of NK cells of 1×10<sup>6</sup>/kg, and the following two patients a dose of 2×10<sup>6</sup>/kg of NK cells. All participants' clinical status and inflammation markers were monitored. No serious adverse events were reported after infusion. Exploratory outcomes included the donor chimerism, NK-cell immunophenotype evolution, and immune lymphocyte reconstitution. This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using NK from COVID-19 convalescent donors is feasible and safe.
Authors
- Alberto Manuel Borobia (ORCID: https://orcid.org/0000-0002-8584-3263)
- José L. Vicário (ORCID: https://orcid.org/0000-0001-6557-1777)
- Rebeca Pérez de Diego (ORCID: https://orcid.org/0000-0001-8426-8765)
- Mercedes Gasior Kabat (ORCID: https://orcid.org/0000-0002-6388-7660)
- Silvia J. Santos (ORCID: https://orcid.org/0000-0002-7067-9851)
- Miguel Ángel Vesga (ORCID: https://orcid.org/0000-0001-5334-0672)
- Miguel Ángel Pérez-Vaquero
- Daniel Lozano‐Ojalvo (ORCID: https://orcid.org/0000-0002-3524-2929)
- Cristina Eguizábal (ORCID: https://orcid.org/0000-0002-8738-2077)
- Bernat Soria (ORCID: https://orcid.org/0000-0002-2356-0380)
- Miguel Ángel Moreno (ORCID: https://orcid.org/0000-0002-3476-2180)
- Antonio Pérez‐Martínez (ORCID: https://orcid.org/0000-0002-6436-9195)
- A. Balas (ORCID: https://orcid.org/0000-0001-7137-3304)
- Pilar Guerra‐García (ORCID: https://orcid.org/0000-0002-7740-0614)
- Leticia Pérez‐Rodríguez (ORCID: https://orcid.org/0000-0002-0311-9643)
- Alejandro Martín‐Quirós (ORCID: https://orcid.org/0000-0003-4630-7668)
- Karima Al‐Akioui‐Sanz (ORCID: https://orcid.org/0009-0008-6656-6468)
- Antonio J. Carcas (ORCID: https://orcid.org/0000-0003-1823-4174)
- Lara Herrera (ORCID: https://orcid.org/0000-0002-5016-3698)
- Clara Hernández-Blanco
- Cristina Aguirre-Portolés
- Jordi Cano-Ochando
Institutions
- Universitat de Miguel Hernández d'Elx (ES)
- Hospital Universitario La Paz (ES)
- Instituto de Salud Carlos III (ES)
- BioCruces Health research Institute (ES)
- Spanish National Cancer Research Centre (ES)
- Hospital La Paz Institute for Health Research (ES)
- Red de Investigación Cardiovascular (ES)
- Osakidetza (ES)
- Comunidad de Madrid (ES)
- Instituto de Investigación en Ciencias de la Alimentación (ES)
- Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) (ES)
- Universidad Autónoma de Madrid (ES)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- iScience
- Published
- 2024-12-27
- DOI
- https://doi.org/10.1016/j.isci.2024.111698
- Citations
- 4
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- article
- Field-Weighted Citation Impact
- 1.48
Funders
- European Commission
- Eusko Jaurlaritza
- Generalitat Valenciana
- CRIS Cancer Foundation
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación