Characterization of IgG N-glycan patterns in COVID-19, sepsis and healthy subjects

Patients with severe infectious diseases may require admission to intensive care units (ICUs) when the infection progresses to severe forms, as observed in sepsis or, more recently, in COVID-19. Despite advances in critical care, the risk of progression toward severe or fatal outcomes remains difficult to predict, highlighting the need for reliable prognostic biomarkers. Immunoglobulin G (IgG) N-glycosylation has emerged as a key modulator of immune responses and may represent a valuable biomarker for assessing disease severity. In this study, we investigated the IgG N-glycans profiles to evaluate their potential association with clinical outcome in critically ill patients with sepsis or COVID-19. Serum IgG N-glycans were characterized using online hydrophilic interaction liquid chromatography (HILIC) solid-phase extraction, followed by HILIC separation and fluorescence and mass spectrometry detection. The study cohort included healthy controls, ICU patients with sepsis or severe COVID-19, the latter being further stratified according to survival outcome. Distinct IgG N-glycosylation patterns and relative abundances of specific N-glycan structures in serum were associated with disease etiology (sepsis versus COVID-19) as well as with patient outcomes for COVID-19 group. These findings suggest that IgG glycosylation profiling may provide a promising approach for stratifying ICU patients according to their risk of developing severe or fatal diseases.