α2,6-Sialylation Is Upregulated in Severe COVID-19, Implicating the Complement Cascade.
ACS Infect Dis
; 8(11): 2348-2361, 2022 Nov 11.
Article
in English
| MEDLINE | ID: covidwho-2185510
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
ACS Infect Dis
Year:
2022
Document Type:
Article
Affiliation country:
Acsinfecdis.2c00421
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