The NIH Lipo-COVID Study: A Pilot NMR Investigation of Lipoprotein Subfractions and Other Metabolites in Patients with Severe COVID-19

A complex interplay exists between plasma lipoproteins and inflammation, as evidenced from studies on atherosclerosis. Alterations in plasma lipoprotein levels in the context of infectious diseases, particularly respiratory viral infections, such as SARS-CoV-2, have become of great interest in recent years, due to their potential utility as prognostic markers. Patients with severe COVID-19 have been reported to have low levels of total cholesterol, HDL-cholesterol, and LDL-cholesterol, but elevated levels of triglycerides. However, a detailed characterization of the particle counts and sizes of the different plasma lipoproteins in patients with COVID-19 has yet to be reported. In this pilot study, NMR spectroscopy was used to characterize lipoprotein particle numbers and sizes, and various metabolites, in 32 patients with severe COVID-19 admitted to the intensive care unit. Our study revealed markedly reduced HDL particle (HDL-P) numbers at presentation, especially low numbers of small HDL-P (S-HDL-P), and high counts of triglyceride-rich lipoprotein particle (TRL-P), particularly the very small and small TRL subfractions. Moreover, patients with severe COVID-19 were found to have remarkably elevated GlycA levels, and elevated levels of branched-chain amino acids and beta-hydroxybutyrate. Finally, we detected elevated levels of lipoproteins X and Z in most participants, which are distinct markers of hepatic dysfunction, and that was a novel finding.