Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 14340
• Main Authors: Trivedi, Vyoma Snehal, Magnusen, Albert Frank, Rani, Reena, Marsili, Luca, Slavotinek, Anne Michele, Prows, Daniel Ray, Hopkin, Robert James, McKay, Mary Ashley, Pandey, Manoj Kumar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.11.2022; MDPI
• Subjects: Chemokines; Complement; Complement C5a - metabolism; Complement component C5a; Complement System Proteins; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Cytokines; Destruction; Gaucher Disease - drug therapy; Gaucher's disease; Glycosphingolipids; Growth factors; Humans; Immune system; Inflammation; innate and adaptive immunity; lipid; Middle East respiratory syndrome; rare-genetic disease; Respiratory diseases; Review; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sphingolipids; Tumor necrosis factor-TNF; viral infection; Middle East; innate and adaptive immunity; viral infection; inflammation; lipid; rare-genetic disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214340

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a-C5aR1-glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a-C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. These results reveal a common involvement of the complement and glycosphingolipid systems driving immune inflammation and tissue damage in COVID-19 and GD, respectively. It is therefore expected that combined targeting of the complement and sphingolipid pathways could ameliorate the tissue destruction, organ failure, and death in patients at high-risk of developing severe cases of COVID-19.