Changes in HDL cholesterol, particles, and function associate with pediatric COVID-19 severity

Abstract

BackgroundMyriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.MethodsA pediatric cohort (N = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified. Clinical data were collected from the medical record and reserve plasma aliquots were assessed for lipoproteins by NMR spectroscopy and assayed for HDL functional cholesterol efflux capacity (CEC). Findings were compared by COVID-19 status and symptom severity. Lipoprotein, NMR spectroscopy and CEC data were compared with 30 outpatient COVID negative children.ResultsDecreasing HDL cholesterol (HDL-c), apolipoprotein AI (ApoA-I), total, large and small HDL particles and HDL CEC showed a strong and direct linear dose-response relationship with increasing severity of COVID-19 symptoms. Youth with mild or no symptoms closely resembled the uninfected. An atypical lipoprotein that arises in the presence of severe hepatic inflammation, lipoprotein Z (LP-Z), was absent in COVID-19 negative controls but identified more often in youth with the most severe infections and the lowest HDL parameters. The relationship between HDL CEC and symptom severity and ApoA-I remained significant in a multiply adjusted model that also incorporated age, race/ethnicity, the presence of LP-Z and of GlycA, a composite biomarker reflecting multiple acute phase proteins.ConclusionHDL parameters, especially HDL function, may help identify youth at risk of more severe consequences of COVID-19 and other novel infectious pathogens.

GlycA: Evaluation of a New Biomarker of Acute Pancreatitis

“…GlycA is also associated with disease severity in pediatric patients with COVID-19. Similar to those with Kawasaki disease, children with multisystem inflammatory syndrome of children (MIS-C) due to SARS-CoV-2 infection also have extremely high levels of GlycA [40]. GlycA levels were also remarkably high in patients with AP in our study, much higher than had been observed in other studies except in studies of adults with sepsis.…”

Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

“…We found profound changes in lipid metabolism, consistent with previous studies 22 , 23 Lipid mediators have been described to be involved in vasodilation and increased vascular permeability 24 , a frequent and severe clinical manifestation of MIS-C 6 . Further, the unsupervised protein-protein co-expression network analyses conducted by machine learning indicated an intricate connection between apolipoproteins and immune dysregulation, which may be due to the function of lipids as proinflammatory mediators, as described in other conditions 25 .…”

Pathogenic mechanisms of cardiovascular damage in COVID-19

“…This lipoprotein can induce a progression of atherosclerotic lesion formation (Julius et al 2022 ). A decrease in apolipoprotein A1 was associated with increased clinical severity in COVID-19 (Mietus-Snyder et al 2022 ). In addition, other lipid particles, including total, large, and small HDL particles, as well as HDL functional cholesterol efflux capacity, were related to the severity of COVID-19 among pediatric patients (Mietus-Snyder et al 2022 ).…”