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Metabolic programs define dysfunctional immune responses in severe COVID-19 patients

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Título

Metabolic programs define dysfunctional immune responses in severe COVID-19 patients

Materia

Descripción

It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells.

Fecha

2021-02-26

Citación

Thompson, Elizabeth A., Katherine Cascino, Alvaro A. Ordonez, Weiqiang Zhou, Ajay Vaghasia, Anne Hamacher-Brady, Nathan R. Brady, Im-Hong Sun, Rulin Wang, Avi Z. Rosenberg, Michael Delannoy, Richard Rothman, Katherine Fenstermacher, Lauren Sauer, Kathyrn Shaw-Saliba, Evan M. Bloch, Andrew D. Redd, Aaron A. R. Tobian, Maureen Horton, Kellie Smith, Andrew Pekosz, Franco R. D'Alessio, Srinivasan Yegnasubramanian, Hongkai Ji, Andrea L. Cox, and Jonathan D. Powell. 2021. "Metabolic programs define dysfunctional immune responses in severe COVID-19 patients." Cell reports:108863-.

Resumen

It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens.

Keywords: COVID-19; MDSCs; SARS-CoV-2; T cells; apoptosis; immunology; immunometabolism; metabolism; mitochondria.

Conflict of interest statement

Declaration of interests J.D.P. is a scientific founder, a paid consultant, and has equity in Dracen Pharmaceuticals.

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