Decoding serum N-Glycome signatures across COVID-19 symptomatic stages

Area of Science:

• Biochemistry
• Immunology
• Glycomics

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection presents diverse clinical outcomes.
• Reliable biomarkers for early risk stratification and severity prediction in COVID-19 are still needed.

Purpose of the Study:

• To characterize serum N-glycome profiles in COVID-19 patients with varying symptom severity and healthy controls.
• To identify potential N-glycan biomarkers for COVID-19 diagnosis and severity assessment.

Main Methods:

• Serum samples were enzymatically deglycosylated.
• N-glycans were analyzed using Hydrophilic Interaction Liquid Chromatography with Fluorescence Detection coupled to a Quadrupole Time-of-Flight Mass Spectrometry (HILIC-FLD-QTOF-MS).
• Case-control comparisons and Receiver Operating Characteristic (ROC) analysis were performed.

Main Results:

• COVID-19 patients showed decreased oligomannose and hybrid-type glycans, with increased tetra-antennary and tetra-galactosylated structures compared to controls.
• Four N-glycan structures demonstrated diagnostic potential for distinguishing COVID-19 from healthy states.
• Severely symptomatic COVID-19 patients exhibited increased antennary fucosylated N-glycans (SLex).
• An isomer of Hex5HexNAc4Neu5Ac showed strong diagnostic potential (AUC > 0.8) for severe COVID-19.

Conclusions:

• Serum N-glycome profiling can differentiate COVID-19 patients from healthy individuals.
• Specific glycan alterations, including antennary fucosylation and Hex5HexNAc4Neu5Ac isomers, are associated with severe COVID-19.
• These findings highlight potential novel biomarkers for COVID-19 risk assessment and severity prediction.