Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
Department of Cell Biology, NYU Grossman School of Medicine, 550 First Avenue, New York, New York 10016, United States.
ACS Infect Dis. 2022 Nov 11;8(11):2348-2361. doi: 10.1021/acsinfecdis.2c00421. Epub 2022 Oct 11.
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.
目前迫切需要更好地了解导致 COVID-19 严重程度的分子机制。尽管过度炎症会导致严重的 COVID-19，但触发这一级联反应的确切机制以及糖基化可能在此过程中发挥的作用尚不清楚。在这里，我们报告了 COVID-19 血浆样本和尸检组织的首次高通量糖组学分析。我们发现，严重 COVID-19 患者的血浆中和尸检肺组织中α2,6-唾液酸化上调。该糖基结构在补体级联反应的成员（例如 C5、C9）上富集，这些成员在严重 COVID-19 中显示出更高的唾液酸化水平。在肺组织中，我们观察到补体沉积增加，与α2,6-唾液酸化水平升高相关，这与预后不良（IL-6）和纤维化反应的标志物升高相对应。我们还观察到 COVID-19 死亡患者中 ST6GAL1 这种α2,6-唾液酸酶的上调。我们的工作确定了严重 COVID-19 中唾液酸化和补体之间以前未描述的关系，这可能为未来的治疗开发提供信息。
