Cell Rep. 2021 Feb 26. pii: S2211-1247(21)00177-7. [Epub ahead of print] 108863
Elizabeth A Thompson,
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,
Jonathan D Powell.
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