Profile of Immunoglobulin G N-Glycome in COVID-19 Patients: A Case-Control Study

Abstract

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.

Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study

“…The serious changes induced in sperm motility by altered tubulin glycosylation have also recently been documented and were alluded to above as part of the important ‘tubulin code’ [ 42 ]. Hence, important work on comparative cannabinoid perturbations of proteomes, phosphoproteomes and post-translational proteomic changes, including altered glycan physiology (as a major post-translational modification) [ 174 , 175 ] and their altered functional metabolomic and epigenomic implications, are similarly large gaps in the literature, which remain to be addressed.…”

IgG N-glycome changes during the course of severe COVID-19: An observational study

“…Recent studies on IgG glycome show that SARS-CoV-2 infection is associated with the decrease in fucosylation of IgG and a low level of IgG sialylation, which triggers ADCC-branch of the immune response and contributes to the elevation of inflammatory cytokines. 9 Also, our previous study on total IgG shows that changes in IgG glycome composition are closely related to the loss of the immunosuppressive function and contribute to the immune-mediated pathologies of SARS-CoV-2 infection. 10 Chakraborty and colleagues show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated anti-RBD IgG1.…”

“…Glycosylation of IgG has been shown to differ between mild and severe COVID-19 cases, as well as between severe COVID-19 cases and healthy controls. 9 IgG consists of two functionally distinct parts, antigen-binding (Fab) and fragment crystallizable (Fc). The Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response.…”

Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors

“…Thus, both an increase in IgG afucosylation [ 44 , 45 ] and a decrease in bisecting N -acetylglucosamine (GlcNAc) and galactosylation were observed in severe COVID-19 patients [ 46 ]. A decrease in sialylation also contributes to enhanced inflammatory activity by ADCC regulation [ 47 ]. The reduced sialylation and galactosylation may play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway.…”