2026-07-24T06:21:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/154432025-04-08T07:37:14Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16988
Repisalud
author
Casado-Fernández, Guiomar
author
Corona, Magdalena
author
Torres, Montserrat
author
Saez, Adolfo J.
author
Ramos-Martín, Fernando
author
Manzanares, Mario
author
Vigon-Hernandez, Lorena
author
Mateos, Elena
author
Pozo Sanchez, Francisco
author
Casas Flecha, Inmaculada
author
García-Gutiérrez, Valentín
author
Rodríguez-Mora, Sara
author
Coiras, Mayte
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Chiesi Foundation
funder
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2023-02-01T14:45:33Z
2023-02-01T14:45:33Z
2023-01
Int. J. Environ. Res. Public Health. 2023, 20(3):1947.
10.3390/ijerph20031947
1660-4601
International Journal of Environmental Research and Public Health
http://hdl.handle.net/20.500.12105/15443
The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) (n = 13) or discharge (Survival group) (n = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome. However, direct cellular cytotoxicity of PBMCs from individuals of the Exitus group against pseudotyped SARS-CoV-2-infected Vero E6 cells was significantly reduced upon admission (−2.69-fold; p = 0.0234) and after 4 weeks at the ICU (−5.58-fold; p = 0.0290), in comparison with individuals who survived, and it did not improve during hospitalization. In vitro treatment with IL-15 of these cells did not restore an effective cytotoxicity at any time point until the fatal outcome, and an increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells. However, IL-15 treatment of PBMCs from individuals of the Survival group significantly increased cytotoxicity at Week 4 (6.18-fold; p = 0.0303). Consequently, immunomodulatory treatments that may overcome immune exhaustion and induce sustained, efficient cytotoxic activity could be essential for survival during hospitalization due to critical COVID-19.
eng
SARS-CoV-2
COVID-19
Immune Response
Cytotoxic response
IL-15
Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome
research article
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