α2,6-Sialylation is Upregulated in Severe COVID-19 Implicating the Complement Cascade.

Area of Science:

• Biochemistry
• Immunology
• Pathology

Background:

• Understanding COVID-19 severity mechanisms is critical.
• Hyper-inflammation is a hallmark of severe COVID-19, but triggers remain unclear.
• The role of glycosylation in COVID-19 pathogenesis is unknown.

Approach:

• First high-throughput glycomic analysis of COVID-19 plasma and autopsy tissues.
• Investigated alpha-2,6-sialylation patterns in severe COVID-19.
• Examined the relationship between sialylation, complement activation, and disease markers.

Key Points:

• Alpha-2,6-sialylation is upregulated in plasma and lung tissue of severe COVID-19 patients.
• This glycan motif is enriched on complement cascade members.
• Increased sialylation correlates with complement deposition, IL-6, and fibrotic markers in lung tissue.
• The ST6GAL1 enzyme is upregulated in fatal COVID-19 cases.

Conclusions:

• Identified a novel link between sialylation and complement activation in severe COVID-19.
• Findings suggest sialylation plays a role in COVID-19-associated hyper-inflammation and pathology.
• This discovery may guide future therapeutic strategies for severe COVID-19.