A new study published in Engineering has uncovered that immunoglobulin G (IgG) fucosylation, a critical type of protein glycosylation, is closely associated with the progression of severe COVID-19, offering new insights into disease pathogenesis and potential therapeutic strategies. The research, conducted by a team of scientists from China, analyzed serum samples from COVID-19 patients and healthy controls, revealing significant changes in fucosylation levels that correlate with disease severity.

The study demonstrated that total serum fucosylation is diminished in COVID-19 patients, with distinct alterations in IgG subtype fucosylation: IgG1 fucosylation increases while IgG2 fucosylation decreases, and the reduction in IgG2 fucosylation is linked to patients’ body temperature and disease progression. Transcriptomic analysis identified 13 differentially expressed genes related to glycosyltransferases and glycosidases in COVID-19 patients, and single-cell sequencing showed that fucosyltransferase family members are expressed in plasma cells and plasmablasts of affected individuals.

Key enzymes regulating these changes are α1,6-fucosyltransferase (FUT8) and α-L-fucosidase 1 (FUCA1), which work in tandem to modulate IgG2 fucosylation during severe COVID-19 development. The research further investigated Fuzheng Jiedu Decoction (FZJDD), a traditional Chinese medicine recommended for severe COVID-19, using network pharmacology and animal experiments. Results indicated that FZJDD may exert its antiviral and anti-inflammatory effects by inhibiting fucosylation; in lipopolysaccharide-induced sepsis mice, the decoction significantly alleviated inflammation and modulated plasma fucosylation levels, mirroring changes observed in human patients.

These findings highlight IgG fucosylation, particularly of the IgG2 subtype, as a meaningful indicator of COVID-19 severity and a potential target for intervention. The regulatory axis of FUT8 and FUCA1 provides a mechanistic framework for understanding glycosylation changes in severe cases, while the effects of FZJDD support the value of defucosylation-targeted approaches in treating severe COVID-19. As glycosylation is a dynamic post‑translational modification sensitive to physiological and pathological states, this work advances glycomedicine research and may guide the development of novel immunomodulatory therapies for severe viral infections.

The paper “IgG Fucosylation: An Emerging Key Player in the Treatment of Severe COVID-19,” is authored by Caiping Zhao, Jingrong Wang, Yuan Liu, Baoling Shang, Danna Lin, Yao Xiao, Hong Ren, Yue Li, Wen Rui, Xu Zou, Hudan Pan, Liang Liu. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.08.004. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.