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Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 May 26; Vol. 12, pp. 665329. Date of Electronic Publication: 2021 May 26 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Vigón, Fuertes, García-Pérez, Torres, Rodríguez-Mora, Mateos, Corona, Saez-Marín, Malo, Navarro, Murciano-Antón, Cervero, Alcamí, García-Gutiérrez, Planelles, López-Huertas and Coiras.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antibodies, Viral blood
Antibodies, Viral immunology
Biomarkers
COVID-19 diagnosis
COVID-19 virology
Comorbidity
Cytokines metabolism
Female
Humans
Immunophenotyping
Leukocytes, Mononuclear metabolism
Male
Middle Aged
Severity of Illness Index
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
COVID-19 epidemiology
COVID-19 immunology
Cytotoxicity, Immunologic
Intensive Care Units
Leukocytes, Mononuclear immunology
Patient Admission statistics & numerical data
SARS-CoV-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34122423
- Full Text :
- https://doi.org/10.3389/fimmu.2021.665329