Abstract
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.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference355 articles.
1. Plasma metabolomic and lipidomic alterations associated with COVID-19;Natl. Sci. Rev.,2020
2. Elevation in sphingolipid upon SARS-CoV-2 infection: Possible implications for COVID-19 pathology;Life Sci. Alliance,2021
3. Inferring a causal relationship between ceramide levels and COVID-19 respiratory distress;Sci. Rep.,2021
4. Torretta, E., Garziano, M., Poliseno, M., Capitanio, D., Biasin, M., Santantonio, T.A., Clerici, M., Caputo, S.L., Trabattoni, D., and Gelfi, C. (2021). Severity of COVID-19 Patients Predicted by Serum Sphingolipids Signature. Int. J. Mol. Sci., 22.
5. COVID-19 and liver disease: Where are we now?;Nat. Rev. Gastroenterol. Hepatol.,2022
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