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

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.

Automated summary

The study identifies a unique population of T cells expressing increased VDAC1 in severe and recovered COVID-19 patients, associated with mitochondrial dysfunction and apoptosis. Additionally, specific metabolic phenotypes of myeloid-derived suppressor cells in COVID-19 patients can distinguish between severe and mild disease. These findings offer insight into dysfunctional immune response in COVID-19 patients and potential for developing personalized therapeutic approaches.