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

Area of Science:

• Immunology
• Glycobiology
• Pathology

Background:

• Hyper-inflammation is a hallmark of severe COVID-19.
• The precise molecular triggers and the role of glycosylation in this process remain unclear.

Purpose of the Study:

• To investigate the role of glycosylation, specifically sialylation, in the molecular mechanisms of severe COVID-19.
• To analyze glycomic alterations in patient plasma and autopsy lung tissues.

Main Methods:

• High-throughput glycomic analysis of plasma samples from COVID-19 patients.
• Analysis of autopsy lung tissues for glycosylation patterns and complement deposition.
• Correlation of sialylation levels with clinical markers and prognosis.

Main Results:

• Upregulation of alpha-2,6-sialylation was observed in the plasma of severe COVID-19 patients and in autopsied lung tissue.
• Elevated alpha-2,6-sialylation was found on complement cascade proteins (C5, C9) in severe cases.
• Increased complement deposition in lung tissue correlated with higher alpha-2,6-sialylation, IL-6, and fibrotic markers.
• The sialylation enzyme ST6GAL1 was upregulated in patients who died from COVID-19.

Conclusions:

• A novel link between alpha-2,6-sialylation and complement activation in severe COVID-19 is identified.
• These findings suggest sialylation as a potential therapeutic target for severe COVID-19.
• The study provides new insights into the molecular pathology of severe COVID-19.