Longitudinal lipoprotein and inflammatory mediators analysis uncover persisting inflammation and hyperlipidemia following SARS-CoV-2 infection in long COVID-19

INTRODUCTION: Individuals suffering from acute COVID-19 (AC) often develop long COVID-19 (LC) syndrome that is associated with aberrant levels of lipoproteins and inflammatory mediators. Yet, these dysregulations are heterogenous due to the uncertain prevalence and require a more extensive characterization. OBJECTIVES: This study aimed to investigate LC-associated dysregulations in inflammatory mediators and lipids by longitudinal Nuclear Magnetic Resonance (NMR) lipoprotein analysis and cytokine profiling in human blood. METHODS: We quantitatively profiled lipoproteins and inflammatory parameters in LC patients at 5 (n = 95), 9 (n = 73), 12 (n = 95), 16 (n = 78), and 20 (n = 85) months post AC by in vitro diagnostics research (IVDr)-based NMR spectroscopy. Simultaneously, we assessed inflammatory meditators with a 13-plex cytokine panel by flow cytometry. We then compared the lipoprotein profiles with historical data from AC (N = 307) and healthy cohorts collected before the COVID-19 pandemic (N = 305), whereas the cytokine profiles were correlated with that of the AC cohort. RESULTS: We identified 31 main and 80 significantly altered subclass lipoproteins, respectively. LC was associated with higher serum levels of very low-density, intermediate-density, low-density, high-density lipoproteins, along with triglycerides, cholesterols, and apolipoprotein a-I & a-II lipoproteins compared to the healthy cohort. We also observed significantly lower concentrations of NMR-based inflammatory parameters in LC than in AC cohort, whilst proinflammatory mediators IFN-α2, IFN-γ, TNF-α, CXCL8/IL-8, IL-12p70, IL-17 A, and IL-23 displayed significantly higher concentrations in LC compared with the AC cohort. Conversely, CCL2/MCP-1, IL-6, and IL-18 were significantly higher in the AC cohort than in LC. CONCLUSION: Our findings demonstrate a persistent hyperlipidemic phenotype in LC alongside signs of chronic inflammation and lipoprotein metabolism that vary in states of acute and chronic inflammation.