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

Guiomar Casado-Fernández, Magdalena Corona, Montserrat Torres, Adolfo J. Saez, Fernando Ramos-Martín, Mario Manzanares, Lorena Vigón, Elena Mateos, Francisco Pozo, Inmaculada Casas, Valentín García-Gutierrez, Sara Rodríguez-Mora () and Mayte Coiras ()
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Guiomar Casado-Fernández: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Magdalena Corona: Faculty of Sciences, Universidad de Alcalá, 28805 Madrid, Spain
Montserrat Torres: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Adolfo J. Saez: Hematology and Hemotherapy Service, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
Fernando Ramos-Martín: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Mario Manzanares: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Lorena Vigón: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Elena Mateos: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Francisco Pozo: Respiratory Viruses Service, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Inmaculada Casas: Respiratory Viruses Service, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Valentín García-Gutierrez: Hematology and Hemotherapy Service, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
Sara Rodríguez-Mora: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain
Mayte Coiras: Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28029 Madrid, Spain

IJERPH, 2023, vol. 20, issue 3, 1-19

Abstract: 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.

Keywords: SARS-CoV-2; COVID-19; immune response; cytotoxic response; IL-15 (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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