2026-05-22T05:27:57Zhttps://repisalud.isciii.es/rest/oai/request

oai: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

00925njm 22002777a 4500 dc 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 author 2023-01 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. 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 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