Glycomic Analysis of Clinical COVID-19 samples identifies alpha-2-6-sialylation as a severity marker and implicates complement cascade

Glycosylation is a key, often forgotten, modulator of the host-response to pathogens. It can control Fc-receptor interactions, downregulate immune responses (via Siglecs) and often acts as a receptor or co-receptor for pathogen interactions. Host response to COVID-19 infection has been varied, ranging from mild symptoms to ARDS and death. Herein, we apply our signature lectin microarray platform to analyze the glycomes of plasma from a range of COVID-19 patients and from autopsy samples. We identify 2-6-sialylation as a marker of severity. This glycan motif was enriched on complement proteins in severe COVID, even when protein levels remained steady. Similar staining patterns were observed for both complement proteins and alpha-2-6-sialic acid in the lungs of COVID-19 patients. Given the emerging importance of complement in COVID-19 progression, our data points to glycosylation of these proteins as an unexplored factor in this disease.