Asunto(s)
COVID-19/diagnóstico , Proteínas de Punto de Control Inmunitario/sangre , Biomarcadores/análisis , Biomarcadores/sangre , COVID-19/sangre , COVID-19/epidemiología , COVID-19/patología , Estudios de Casos y Controles , Comorbilidad , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/epidemiología , Síndrome de Liberación de Citoquinas/etiología , Servicio de Urgencia en Hospital , Femenino , Humanos , Proteínas de Punto de Control Inmunitario/análisis , Masculino , Mortalidad , Admisión del Paciente , Pronóstico , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)-related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.
Asunto(s)
COVID-19 , SARS-CoV-2 , Tolerancia a Endotoxinas , Genes MHC Clase II , Humanos , ARN ViralRESUMEN
We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.