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Published on: October 20, 2023
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.
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.
Abstract:
Better understanding of the molecular mechanisms underlying COVID-19 severity is desperately needed in current times. Although hyper-inflammation drives severe COVID-19, precise mechanisms triggering this cascade and what role glycosylation might play therein are unknown. Here we report the first high-throughput glycomic analysis of COVID-19 plasma samples and autopsy tissues. We find that α2,6-sialylation is upregulated in the plasma of patients with severe COVID-19 and in autopsied lung tissue. This glycan motif is enriched on members of the complement cascade (e.g., C5, C9), which show higher levels of sialylation in severe COVID-19. In the lung tissue, we observe increased complement deposition, associated with elevated α2,6-sialylation levels, corresponding to elevated markers of poor prognosis (IL-6) and fibrotic response. We also observe upregulation of the α2,6-sialylation enzyme ST6GAL1 in patients who succumbed to COVID-19. Our work identifies a heretofore undescribed relationship between sialylation and complement in severe COVID-19, potentially informing future therapeutic development.
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