Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study

N. Hoertel (1, 2, 3) , M. Sánchez-Rico (2, 3, 4) , E. Gulbins (5) , J. Kornhuber (6) , Alexander Carpinteiro (5) , Miriam Abellán (2, 3) , Pedro de La Muela (2, 3, 4) , R. Vernet (7) , N. Beeker (8) , A. Neuraz (9, 10) , J. Alvarado (4) , C. Cougoule (11) , P. Meneton (12) , Frédéric Limosin (2, 1)

1 IPNP - U1266 Inserm - Institut de psychiatrie et neurosciences de Paris
2 Hôpital Corentin Celton [Issy-les-Moulineaux]
3 DMU Psychiatrie et Addictologie [Hôpital Corentin Celton, Issy-les-Moulineaux]
4 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
5 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
6 FAU - Friedrich–Alexander University Erlangen–Nürnberg
7 HEGP - Hôpital Européen Georges Pompidou [APHP]
8 Hôpital Cochin [AP-HP]
9 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
10 Hôpital Necker - Enfants Malades [AP-HP]
11 IPBS - Institut de pharmacologie et de biologie structurale
12 LIMICS - Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé

Abstract The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.1%) received a FIASMA psychotropic medication upon hospital admission for COVID-19. We compared the composite endpoint of intubation or death between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and other medications. FIASMA psychotropic medication use at baseline was significantly associated with reduced risk of intubation or death in both crude (HR = 0.42; 95%CI = 0.31–0.57; p < 0.01) and primary inverse probability weighting (IPW) (HR = 0.50; 95%CI = 0.37–0.67; p < 0.01) analyses. This association was not specific to one FIASMA psychotropic class or medication. Patients taking a FIASMA antidepressant at baseline had a significantly reduced risk of intubation or death compared with those taking a non-FIASMA antidepressant at baseline in both crude (HR = 0.57; 95%CI = 0.38–0.86; p < 0.01) and primary IPW (HR = 0.57; 95%CI = 0.37–0.87; p < 0.01) analyses. These associations remained significant in multiple sensitivity analyses. Our results show the potential importance of the ASM/ceramide system framework in COVID-19 and support the continuation of FIASMA psychotropic medications in these patients and the need of large- scale clinical trials evaluating FIASMA medications, and particularly FIASMA antidepressants, against COVID-19.

Domaines: Informatique et langage [cs.CL]

N. Hoertel, M. Sánchez-Rico, E. Gulbins, J. Kornhuber, Alexander Carpinteiro, et al.. Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study. Translational Psychiatry, 2022, 12 (1), pp.90. ⟨10.1038/s41398-022-01804-5⟩. ⟨hal-03650036⟩