Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19

on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium

doi:10.3390/jcm11195882

Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19

on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium

Medicine - Infectious Disease and International Medicine

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP–HP (Assistance Publique–Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35–0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41–0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.

Original language	English (US)
Article number	5882
Journal	Journal of Clinical Medicine
Volume	11
Issue number	19
DOIs	https://doi.org/10.3390/jcm11195882
State	Published - Oct 2022

Bibliographical note

Funding Information:
N.H., M.S.R., J.K., E.G., A.C., C.M. and F.L. are inventors on a patent application related to methods of treating COVID-19, filled by Assistance Publique—Hopitaux de Paris in France. N.H. has received personal fees and non-financial support from Lundbeck, outside the submitted work. C.L. has received personal fees and non-financial support from Lundbeck and Otsuka Pharmaceutical, outside the submitted work. E.L. has received grant support (non-federal) from COVID Early Treatment Fund, Mercatus Center Emergent Ventures, the Skoll Foundation, the Taylor Family Institute for Innovative Psychiatric Research, the Center for Brain Research in Mood Disorders, the Patient-Centered Outcomes Research Institute, Janssen, and the Barnes Jewish Foundation, and has received consulting fees from Janssen and Jazz Pharmaceuticals. A.R. has received grant or research support from the McDonnell Center for Systems Neuroscience, the McDonnell Center for Cellular and Molecular Neurobiology, and the Taylor Family Institute for Innovative Psychiatric Research. A.R. and E.L. are inventors on a patent application related to methods of treating COVID-19, which was filed by Washington University in St. Louis. Other authors declare no conflict of interest related to this work.

Publisher Copyright:
© 2022 by the authors.

Keywords

COVID-19
FIASMA
SARS-CoV-2
antidepressant
ceramide
fluoxetine
fluvoxamine
mortality
sigma-1 receptor
sphingomyelinase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/jcm11195882

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on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium (2022). Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19. Journal of Clinical Medicine, 11(19), Article 5882. https://doi.org/10.3390/jcm11195882

Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19. / on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium.
In: Journal of Clinical Medicine, Vol. 11, No. 19, 5882, 10.2022.

Research output: Contribution to journal › Article › peer-review

on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium 2022, 'Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19', Journal of Clinical Medicine, vol. 11, no. 19, 5882. https://doi.org/10.3390/jcm11195882

on behalf of AP-HP/Université Paris Cité/INSERM COVID-19 Research Collaboration, AP-HP COVID CDR Initiative and “Entrepôt de Données de Santé” AP-HP Consortium. Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19. Journal of Clinical Medicine. 2022 Oct;11(19):5882. doi: 10.3390/jcm11195882

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title = "Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19",

abstract = "To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP–HP (Assistance Publique–H{\^o}pitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35–0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41–0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.",

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note = "Funding Information: N.H., M.S.R., J.K., E.G., A.C., C.M. and F.L. are inventors on a patent application related to methods of treating COVID-19, filled by Assistance Publique—Hopitaux de Paris in France. N.H. has received personal fees and non-financial support from Lundbeck, outside the submitted work. C.L. has received personal fees and non-financial support from Lundbeck and Otsuka Pharmaceutical, outside the submitted work. E.L. has received grant support (non-federal) from COVID Early Treatment Fund, Mercatus Center Emergent Ventures, the Skoll Foundation, the Taylor Family Institute for Innovative Psychiatric Research, the Center for Brain Research in Mood Disorders, the Patient-Centered Outcomes Research Institute, Janssen, and the Barnes Jewish Foundation, and has received consulting fees from Janssen and Jazz Pharmaceuticals. A.R. has received grant or research support from the McDonnell Center for Systems Neuroscience, the McDonnell Center for Cellular and Molecular Neurobiology, and the Taylor Family Institute for Innovative Psychiatric Research. A.R. and E.L. are inventors on a patent application related to methods of treating COVID-19, which was filed by Washington University in St. Louis. Other authors declare no conflict of interest related to this work. Publisher Copyright: {\textcopyright} 2022 by the authors.",

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AB - To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP–HP (Assistance Publique–Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35–0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41–0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.

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Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19

Abstract

Bibliographical note

Keywords

UN SDGs

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