Distinct metabolomic profiles and systemic lipid dysregulation in longitudinal analysis of COVID-19 disease trajectory and long COVID outcomes 2785

Abstract Description The Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a longitudinal study of 1,132 hospitalized COVID-19 patients across the US aimed at identifying molecular signatures associated with acute disease trajectory during inpatient stay and post-acute sequelae (PASC) assessed by patient-reported outcomes (PRO) over 28 days and up to one- year post-discharge. Global metabolomics using liquid chromatography-tandem mass spectrometry identified 578 metabolites across 4,140 samples to uncover therapeutic targets and biomarkers for dynamic insights into disease progression. Metabolomics data were analyzed using multivariate statistical approaches and differential abundance testing to identify significantly altered metabolites. Baseline analyses identified key metabolites linked to inflammation and early disease severity, with pathway analysis highlighting disruptions in amino acid, lipid, carbohydrate, and nucleotide metabolism. Tryptophan metabolism showed consistent trends. Longitudinal changes were assessed using mixed-effects modeling to capture dynamic lipid dysregulation, particularly in phospholipid and sphingolipid metabolism. Reduced phosphatidylcholines were linked to PRO deficits post-discharge, suggesting associations with PASC severity. These findings highlight the potential of metabolomics to uncover critical biomarkers and therapeutic targets for COVID-19, driving deeper understanding of disease mechanisms and recovery trajectories. Funding Sources NIH (3U01AI167892-03S2, 3U01AI167892-01S2, 5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI057229-18, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, and 5T32DA018926-18, 3U19AI1289130, U19AI128913-04S1, and R01AI122220, UM1TR004528); NSF DMS2310836 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)