Links between COVID-19, long COVID and neurodegeneration: the role of glycosphingolipids

Journal article

Glycosphingolipids (GSLs) play major roles in viral infections, via viral entry and egress from cells in lipid rafts, but GSLs are also important in neurodegenerative diseases. The role of GSLs in acute COVID-19 infection is critical, although less studied in the sequelae of long COVID (Post-COVID Condition), but as the same enzymes controlling GSL metabolism are critical for viral entry and exit, neuromuscular junctions, neurological function, and cellular metabolism, it is important to define whether long COVID may increase the risk of subsequent neurodegeneration. SARSCoV-2 infection changes lipid metabolism, oxygen use, and can bind to and modify the expression of neurotrophic GSLs such as GM1 ganglioside. GM1 (Neu5Ac) is humanspecific, probably evolved as a result of a pandemic 3 - 2.5 million years ago that drove its selection. GM1 is a co-receptor with ACE2 for SARS-CoV-2, while also being a neurotrophin. Viral multiplication takes place in the endoplasmic reticulum/Golgi apparatus where GSLs are synthesized. This review defines the complex interaction between viruses, GSLs and neurodegeneration, which provides new perspectives on the interlinked metabolic changes. A European working group has been set up to assess risks of neurodegeneration with long COVID, based on potential GSL-mediated mechanisms.

Authors: Spedding, M; Aerts, J; Alexander, S; Platt, FM; Talbot, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Pharmacological Reviews
• Volume: 78
• Issue: 2
• Article number: 100113
• Publication date: 2026-01-29
• Acceptance date: 2025-12-29
• DOI: 10.1016/j.pharmr.2026.100113
• EISSN: 1521-0081
• ISSN: 0031-6997
• Language: English