PhD Student La Jolla Institute for Immunology La Jolla, California, United States
Introduction/Rationale: Long COVID, defined as symptoms persisting for three months or longer following acute SARS-CoV-2 infection, represents a substantial and growing public health burden with limited therapeutic options. Progress in diagnosis and treatment is impeded by clinical heterogeneity, a lack of actionable biomarkers, and the absence of FDA-approved therapeutics. Here, we aimed to characterize alterations in lipid metabolite profiles and circulating cytokine profiles in long COVID.
Methods: We analyzed infection-naïve and vaccine-naïve individuals with long COVID sampled during the first wave of the COVID-19 pandemic enrolled in the Cedars-Sinai CORALE-EMBARC study. We focused on individuals reporting neurocognitive symptoms, reasoning that symptom-specific cohorts may enable more precise identification of underlying molecular drivers. Long COVID participants were defined as reporting at least one neurocognitive symptom following SARS-CoV-2 infection and were compared to age- and sex-matched never-infected or COVID-recovered participants (n=135 total). Immune and metabolic profiles were assessed through multiplex serum cytokine analysis and untargeted LC-MS/MS.
Results: Untargeted plasma lipidomics revealed distinct lipid signatures that differentiated COVID-recovered and neurocognitive long COVID groups following multivariate logistic regression analysis adjusted for age and sex. Lipid metabolite changes included reductions of anti-inflammatory mediators. Interestingly, we did not observe widespread elevations in circulating proinflammatory cytokines in individuals with neurocognitive long COVID.
Conclusion: These findings suggest that circulating proinflammatory cytokine levels may not reliably distinguish neurocognitive long COVID from COVID-recovered individuals. Instead, we found neurocognitive long COVID to be characterized by distinct lipidomic alterations, implicating lipid mediators as potential contributors to disease pathophysiology and highlighting their promise as therapeutic targets.
