Investigating the role of mitochondrial dysfunction and inflammation in the post-COVID19 condition

SARS-CoV-2, identified in 2019, is a multisystemic illness that has resulted in approximately 780 million infections worldwide. A subgroup of COVID-19 patients have lingering symptoms, including significant fatigue, shortness of breath, post-exertional malaise, and cognitive impairment. This chronic condition, referred to as the "post COVID-19 condition" or "long COVID" (LCOV), has several phenotypic similarities to other genetic disorders. Recent evidence implicates inflammation and mitochondrial dysfunction in the pathogenesis of long COVID. Lymphopenia has been reported to affect CD4+ and CD8+ cells in COVID-19, and these resident T cells increase their utilization of major energy pathways in response to immune challenge. Understanding T cell respiration can reveal how energy production and utilization in these immune cells are altered in long COVID, potentially identifying targets for therapeutic intervention. We will examine blood drawn from the antecubital vein from healthy age- and sex-matched controls (n=20) LCOV (n=20) patients. T cells will be subsequently isolated into CD4+ and CD8+ cells by magnetic-activated cell sorting (MACS). Our research aims to (1) investigate immunometabolism in LCOV by analyzing mitochondrial respiration and dynamics in T cell subsets, (2) examine blood-borne inflammatory markers that contribute to LCOV and mitochondrial dysregulation and (3) identify and correlate components of respiratory function, body composition and overall fitness level to severity of LCOV symptoms and T cell outcomes. We hypothesize that decreased metabolic function of the T cells, as measured by in vitro oxidation consumption rate will be related not only to poor mitochondrial morphology but also poor respiratory function.