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

Rui Qin1, Emma Kurz2, Shuhui Chen3

  • 1Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.

ACS Infectious Diseases
|October 11, 2022
PubMed

Insights

Severe COVID-19 involves increased alpha-2,6-sialylation, a sugar modification, particularly on complement proteins in plasma and lung tissue. This finding may guide new COVID-19 therapies.

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.

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