SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19.
José Avendaño-OrtizRoberto Lozano-RodríguezAlejandro Martín-QuirósCharbel Maroun-EidVerónica Terrón-ArcosKarla Montalbán-HernándezJaime ValentínElena Muñoz Del ValMiguel A García-GarridoÁlvaro Del Balzo-CastilloJosé Carlos Casalvilla-DueñasMaría PeinadoLaura GómezCarmen Herrero-BenitoCarolina RubioCarolina Cubillos-ZapataAlejandro Pascual-IglesiasCarlos Del Fresno SánchezLuis Augusto AguirreEduardo López-CollazoPublished in: Journal of immunology (Baltimore, Md. : 1950) (2021)
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.