α2,6-Sialylation Is Upregulated in Severe COVID-19, Implicating the Complement Cascade
Rui Qin, Emma Kurz, Shuhui Chen, Briana Zeck, Luis Chiribogas, Dana Jackson, Alex Herchen, Tyson Attia, Michael A. Carlock, Amy Rapkiewicz, Dafna Bar‐Sagi, Bruce Ritchie, Ted M. Ross, Lara K. Mahal
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.