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Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity.
Vigón, Lorena; Fuertes, Daniel; García-Pérez, Javier; Torres, Montserrat; Rodríguez-Mora, Sara; Mateos, Elena; Corona, Magdalena; Saez-Marín, Adolfo J; Malo, Rosa; Navarro, Cristina; Murciano-Antón, María Aranzazu; Cervero, Miguel; Alcamí, José; García-Gutiérrez, Valentín; Planelles, Vicente; López-Huertas, María Rosa; Coiras, Mayte.
  • Vigón L; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Fuertes D; School of Telecommunications Engineering, Universidad Politécnica de Madrid, Madrid, Spain.
  • García-Pérez J; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Torres M; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Rodríguez-Mora S; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Mateos E; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Corona M; Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain.
  • Saez-Marín AJ; Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain.
  • Malo R; Neumology Service, Hospital Universitario Puerta de Hierro, Majadahonda, Spain.
  • Navarro C; Neumology Service, Hospital de El Escorial, El Escorial, Spain.
  • Murciano-Antón MA; Family Medicine, Centro de Salud Doctor Pedro Laín Entralgo, Alcorcón, Spain.
  • Cervero M; Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain.
  • Alcamí J; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • García-Gutiérrez V; Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain.
  • Planelles V; Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT, United States.
  • López-Huertas MR; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • Coiras M; Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
Front Immunol ; 12: 665329, 2021.
Article in English | MEDLINE | ID: covidwho-1268251
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Patient Admission / Leukocytes, Mononuclear / Cytotoxicity, Immunologic / SARS-CoV-2 / COVID-19 / Intensive Care Units Type of study: Diagnostic study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.665329

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Patient Admission / Leukocytes, Mononuclear / Cytotoxicity, Immunologic / SARS-CoV-2 / COVID-19 / Intensive Care Units Type of study: Diagnostic study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.665329