SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19.

Avendaño-Ortiz, José; Lozano-Rodríguez, Roberto; Martín-Quirós, Alejandro; Maroun-Eid, Charbel; Terrón-Arcos, Verónica; Montalbán-Hernández, Karla; Valentín, Jaime; Muñoz Del Val, Elena; García-Garrido, Miguel A; Del Balzo-Castillo, Álvaro; Casalvilla-Dueñas, José Carlos; Peinado, María; Gómez, Laura; Herrero-Benito, Carmen; Rubio, Carolina; Cubillos-Zapata, Carolina; Pascual-Iglesias, Alejandro; Del Fresno, Carlos; Aguirre, Luis A; López-Collazo, Eduardo

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.