SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes, which can be prevented by atazanavir.

Ferreira, A. C.; Soares, V. C.; Quintanilha, I. G. d. A.; Dias, S. d. S. G.; Rodrigues, N. F.; Sacramento, C. Q.; Mattos, M.; Freitas, C. S.; Temerozo, J. R.; Teixeira, L.; Hottz, E. D.; Barreto, E.; Pao, C. R.; Palhinha, L.; Miranda, M.; Bou-Habib, D. C.; Bozza, F. A.; Bozza, P. T.; Lopes e Souza, T. M.

Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocytes death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and in patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1beta production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe the mechanism by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb in patients with severe 2019 coronavirus disease (COVID-19), and emphasize the need for identifying anti-inflammatory and antiviral strategies to prevent SARS-CoV-2-induced pyroptosis.