| Autor: |
Qin R; Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada., Kurz E; Department of Cell Biology, NYU Grossman School of Medicine, 550 First Avenue, New York, New York 10016, United States., Chen S; Department of Chemistry, Biomedical Research Institute, New York University, New York, New York10003, United States., Zeck B; Center for Biospecimen Research and Development, NYU Langone, New York, New York 10016, United States., Chiribogas L; Center for Biospecimen Research and Development, NYU Langone, New York, New York 10016, United States., Jackson D; University of Alberta Hospital, Edmonton, Alberta T6G 2B7, Canada., Herchen A; University of Alberta Hospital, Edmonton, Alberta T6G 2B7, Canada., Attia T; University of Alberta Hospital, Edmonton, Alberta T6G 2B7, Canada., Carlock M; Center for Vaccines and Immunology, University of Georgia, Athens, Georgia 30605, United States., Rapkiewicz A; Department of Pathology, NYU Long Island School of Medicine, Mineola, New York 11501, United States., Bar-Sagi D; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, New York 10016, United States., Ritchie B; University of Alberta Hospital, Edmonton, Alberta T6G 2B7, Canada., Ross TM; Center for Vaccines and Immunology, University of Georgia, Athens, Georgia 30605, United States., Mahal LK; Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada. |
| Abstrakt: |
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. |
