Post-COVID impairment of memory T cell responses to community-acquired pathogens is associated with underlying metabolic dysfunction 2304057
TL;DR
It is demonstrated that decreased mitochondrial function in T cells post-COVID may contribute to higher infection susceptibility by metabolically immobilizing T cell memory responses and indicate that COVID-19 infection may have lasting effects on inhibiting T cell memory responses to common community-acquired pathogens.
Abstract
Infection rates involving bacterial and viral pathogens have increased precipitously after the COVID-19 pandemic, but why rates remain high today is unclear. Mitochondrial dysfunction is known to occur post-COVID and may disrupt immune responses. Within T cells, SARS-CoV-2 infection is linked to low mitochondrial membrane potential, increased mitochondrial apoptosis, and decreased mitochondrial respiration, which together impact cellular activation and function beyond the acute phase of illness. Here, we demonstrate that decreased mitochondrial function in T cells post-COVID may contribute to higher infection susceptibility by metabolically immobilizing T cell memory responses. Using donor-matched peripheral blood samples from COVID-naïve individuals who subsequently contracted COVID-19, we tracked how influenza A (IAV), Staphylococcus aureus (SA), and varicella-zoster virus (VZV) T memory cell responses are impacted by SARS-Cov-2 infection using RNA-Seq and flow cytometry. We found that gene expression linked to T cell activation decreased but mitochondrial redox-pathway genes increased in CD4 memory T cells post-COVID. We also observed a disordered relationship between memory T cell mobilization of glycolysis, fatty acid metabolism, and oxidative phosphorylation pathways post-COVID. Collectively, these findings indicate that COVID-19 infection may have lasting effects on inhibiting T cell memory responses to common community-acquired pathogens, with implications for the clinical care of immunologically vulnerable populations in the post-pandemic era. Balvi Ops Grant B48 Immune Mechanisms of Human Disease (HUM)