This study investigated the impact of peripheral blood mononuclear cell (PBMC) cytotoxic activity on the outcome of unvaccinated individuals with critical COVID-19 in the ICU. Blood samples were collected from 23 individuals upon admission and every 2 weeks for 13 weeks. The Exitus group (n=13) comprised those who died, and the Survival group (n=10) those who were discharged. No significant differences were found between groups in sociodemographic, clinical, or biochemical data. However, PBMC cytotoxicity against SARS-CoV-2-infected Vero E6 cells was significantly reduced in the Exitus group upon admission and after 4 weeks, and did not improve during hospitalization. IL-15 treatment did not restore cytotoxicity in the Exitus group, while it significantly increased cytotoxicity in the Survival group at Week 4. Increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells in the Exitus group. Immunomodulatory treatments to overcome immune exhaustion and induce sustained cytotoxic activity are suggested as essential for survival in critical COVID-19.

Giovanni Orsi, 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, Mayte Coiras