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

Abstract

By interrogating metabolic programs in the peripheral blood mononuclear cells (PBMC) of acutely infected COVID-19 patients, we identified novel and distinct immune cell subsets Our studies identified a non-clonal population of T cells expressing high H3K27me3 and voltage-dependent anion channel (VDAC) with mitochondrial dysfunction and increased susceptibility to cell death. Characterized by dysmorphic mitochondria and increased cytoplasmic cytochrome c , apoptosis of these cells was inhibited by preventing VDAC aggregation or blocking caspase activation. Further, we observed a marked increase in Hexokinase II + polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC). While PMN-MDSC were also found in the PBMC of patients with other viral infections, the Hexokinase II + PMN-MDSC were found exclusively in the acute COVID-19 patients with moderate or severe disease. Finally, we identified a population of monocytic MDSC (M-MDSC) expressing high carnitine palmitoyltransferase I (CPT1a) and VDAC, which were present in the PBMC of the acute COVID-19 patients, but not recovered COVID-19 patients and whose presence correlated with severity of disease. Overall, these unique populations of immune cells provide insight into the pathogenesis of SARS-CoV-2 infection and provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel therapeutic regimens. One Sentence Summary Metabolic programs define unique immune cells among COVID-19 patients with severe diease.

Cited by papers we hold 5

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• T Cell Metabolism in Infection · 2022
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• Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good · 2022
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• Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19 · 2021
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• Monocytes and Macrophages in COVID-19 · 2021
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