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

• DOI: 10.1021/acsinfecdis.2c00421
• Publication Date: 2022-10-11T17:08:16Z
• Authors: Rui Qin; Emma Kurz; Shuhui Chen; Briana Zeck; Luis Chiribogas; Dana Jackson; Alex Herchen; Tyson Attia; Michael Carlock; Amy Rapkiewicz; Dafna Bar-Sagi; Bruce Ritchie; Ted M. Ross; Lara K. Mahal
• Keywords: Glycosylation; Polysaccharides; Humans; COVID-19; Article; 3. Good health

ABSTRACTBetter understanding of the mechanisms of 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 is unknown. Here we report the first high-throughput glycomic analysis of COVID-19 plasma samples and autopsy tissues. We find α2,6-sialylation is upregulated in plasma of patients with severe COVID-19 and in the lung. This glycan motif is enriched on members of the complement cascade, 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.