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Study on the role of “ceramides” in infection by SARS-CoV-2 which could constitute a biomarker of severity and a therapeutic target in the management of Covid-19

13 Oct 2021 | By INSERM (Newsroom) | Covid-19



Electron microscopy of a cell infected with SARS-CoV-2 © Philippe Roingeard, Anne Bull-Maurer, Sonia Georgeault, unité Inserm U1259 MAVIVH & Université de Tours, France.


Teams from the psychiatry and addictology department of the Corentin-Celton AP-HP hospital, the University of Paris and Inserm in collaboration with the University of Erlangen-Nuremberg and the University of Duisburg-Essen , coordinated by Dr Nicolas Hoertel, Prof Jo hannes Kornhuber and Prof Erich Gulbins, published on October 4, 2021 in the journal Molecular Psychiatry (Nature Publishing Group) a summary of the results of the international literature on the central role that “ ceramides ”, a class of lipids, may play a role in SARS-CoV-2 infection.

Results from in vitro data [1, 2] indicate that an enzyme found in cell lysosomes, acid sphingomyelinase (ASM), is activated by the virus upon binding to its ACE-2 cell receptor, inducing synthesis of a specific class of lipids, the “ceramides”, in the membrane of cells. These studies [1, 2] demonstrate that these ceramides serve as a gateway for the virus to infect cells.

Indeed, the reduction in the quantity of ceramides by functional inhibitors of ASM (called FIASMA, comprising in particular certain antidepressants such as fluoxetine or else fluvoxamine) or the use of anti-ceramide antibodies make it possible to greatly reduce infection in vitro according to these same studies [1-2] .

In addition, clinical data [3, 4] indicate that elevated plasma levels of ceramides are significantly and strongly associated with the clinical severity of infection and the severity of inflammation in patients with Covid-19.

Finally, preclinical [1, 2, 5, 6] , observational [7-9] and three clinical trials [10-12] , including two randomized placebo-controlled trials [10, 12] , conclude on potentially strong efficacy of fluvoxamine and fluoxetine against Covid-19. Several clinical trials using fluvoxamine or fluoxetine, necessary to confirm these very encouraging results, are underway in several countries (United States, Canada, South Africa, Brazil and Croatia).

This publication concludes that the activity of the enzyme ASM and the plasma levels of ceramides could allow a better understanding of this infection and its risk factors for poor prognosis, as well as the antiviral, anti-inflammatory and clinical effects observed with drugs that are functional ASM inhibitors, including fluoxetine and fluvoxamine.



  1. Carpinteiro, A. et al. Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells. Cell Rep. Med. 100142 (2020).
  2. Carpinteiro, A. et al. Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. J. Biol. Chem. 100701 (2021). doi: 10.1016 / j.jbc.2021.100701
  3. Marín-Corral J, Rodríguez-Morató J, Gomez-Gomez A, Pascual-Guardia S, Muñoz-Bermúdez R, Salazar-Degracia A, et al. Metabolic signatures associated with severity in hospitalized COVID-19 patients. Int J Mol Sci. 2021; 22: 4794.
  4. Khodadoust, M. Ceramide levels and COVID-19 respiratory distress, a causal relationship. Research Square. 2021. .
  5. Schloer, S. et al. Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine. Emerg. Microbes Infect. 9, 2245–2255 (2020).
  6. Zimniak M. et al. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue. Sci Rep. 2021 Mar 15; 11 (1): 5890.
  7. Hoertel, N. et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol. Psychiatry (2021) .doi: 10.1038 / s41380-021-01021-4
  8. Diez-Quevedo C et al. Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients. Acta Psychiatr Scand. 2021 Jun; 143 (6): 526-534.
  9. Hoertel, N. et al. Association between FIASMAs and reduced risk of intubation or death in individuals hospitalized for severe COVID-19: an observational multicenter study. Clin Pharmacol Ther. 2021. .
  10. Lenze, EJ et al. Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA 324, 2292–2300 (2020).
  11. Seftel, D. & Boulware, DR Prospective Cohort of Fluvoxamine for Early Treatment of Coronavirus Disease 19. Open Forum Infect. Say. 8, ofab050 (2021).
  12. Reis, G., et al. Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial. medRxiv . 2021; .

The acid sphingomyelinase/ceramide system in COVID-19. Molecular Psychiatry. 2021.

Kornhuber J, Hoertel N, Gulbins E