{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:02:20Z","timestamp":1777507340425,"version":"3.51.4"},"reference-count":355,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013C5aR1\u2013glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a\u2013C5aR1 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.<\/jats:p>","DOI":"10.3390\/ijms232214340","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Targeting the Complement\u2013Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy"],"prefix":"10.3390","volume":"23","author":[{"given":"Vyoma Snehal","family":"Trivedi","sequence":"first","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert Frank","family":"Magnusen","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reena","family":"Rani","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-9911","authenticated-orcid":false,"given":"Luca","family":"Marsili","sequence":"additional","affiliation":[{"name":"Department of Neurology, James J. and Joan A. Gardner Center for Parkinson\u2019s Disease and Movement Disorders, University of Cincinnati, 3113 Bellevue Ave, Cincinnati, OH 45219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Michele","family":"Slavotinek","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, 3230 Eden Ave, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Ray","family":"Prows","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, 3230 Eden Ave, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert James","family":"Hopkin","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, 3230 Eden Ave, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5412-0986","authenticated-orcid":false,"given":"Mary Ashley","family":"McKay","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0495-830X","authenticated-orcid":false,"given":"Manoj Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, Building R1, MLC 7016, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, 3230 Eden Ave, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/nsr\/nwaa086","article-title":"Plasma metabolomic and lipidomic alterations associated with COVID-19","volume":"7","author":"Wu","year":"2020","journal-title":"Natl. 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