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Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study
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  • Published: 22 January 2026

Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study

  • Charlène Lefèvre  ORCID: orcid.org/0000-0001-7349-61131,
  • Théo Funck-Brentano1,
  • Marine Cachanado  ORCID: orcid.org/0000-0002-9739-79502,
  • Alexia Plocque  ORCID: orcid.org/0000-0003-0932-67391,
  • Maëlle Youinou  ORCID: orcid.org/0009-0002-9285-62032,
  • Audrey Fels  ORCID: orcid.org/0000-0001-5179-76442,
  • Frédéric Pène  ORCID: orcid.org/0000-0003-3639-38493,4,
  • Laurent Savale  ORCID: orcid.org/0000-0002-6862-89755,6,
  • David Montani  ORCID: orcid.org/0000-0002-9358-69225,6,
  • Olivier Voisin  ORCID: orcid.org/0000-0001-6802-95457,
  • Flore Bintein  ORCID: orcid.org/0000-0002-0202-67368,
  • Lucille Wildenberg  ORCID: orcid.org/0000-0002-0438-51699,
  • Axel Philippe10,
  • Stéphane Legriel  ORCID: orcid.org/0000-0003-4782-673411,12,
  • Nicolas Roche  ORCID: orcid.org/0000-0002-3162-503313,
  • Pierre-Régis Burgel  ORCID: orcid.org/0000-0003-0903-982814,15,
  • Marc Tran1,
  • Nicolas Noël  ORCID: orcid.org/0000-0003-4055-617X16,
  • Christophe Baillard  ORCID: orcid.org/0000-0003-3093-137810,
  • Jacques Duranteau  ORCID: orcid.org/0000-0003-1902-26249,
  • Gilles Chatellier  ORCID: orcid.org/0000-0002-6373-89562 &
  • …
  • Francois Philippart  ORCID: orcid.org/0000-0002-7323-07421,17 

Scientific Reports , Article number:  (2026) Cite this article

  • 265 Accesses

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Infectious diseases
  • Outcomes research
  • Phase IV trials
  • Viral infection

Abstract

During severe and critical COVID-19, therapeutic options remain scarce. Among interventions, the use of interleukin-6 receptor inhibitor (IL-6Ri) is especially controversial due to persistent uncertainty about their efficacy and safety. To compare the occurrence of secondary infections, digestive and hematological complication function of the administration of IL-6Ri we conducted a multicentric retrospective French observational study. All severe or critical COVID-19 requiring hospital admission were included. Among 2587 patients requiring hospital admission, 1603 had a severe COVID-19 and 984 a critical one requiring ICU admission. 224 received at least one dose of tocilizumab or sarilumab. Incidence of secondary infection was 29.5% in the IL-6Ri group vs. 19.5% without IL-6Ri (p = 0.0004) in the whole population. This result remained consistent after adjustment, without multiple imputation (MI) and after MI (adjusted OR: 1.47 [1.25; 1.72]; p < 0.0001)). Incidence of hematological or digestive complication were similar between groups. Mortality of patients admitted in ward was higher in the IL-6Ri group (18.7% vs 10.5%, p = 0.0155). No difference in 28 days, ICU, hospital of 90 days mortality was noticed among ICU patients.

Clinical trial registration: This study was registred on ClinicalTrial.gov: NCT05017441.

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Data availability

Datasets used/analyzed in this study are accessible upon reasonable request to the corresponding author.

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Acknowledgements

This work was supported by the Groupe Hospitalier Paris Saint‑Joseph All data generated or analyzed during this study are included in this study or its supplementary material files. Further inquiries can be directed to the corresponding author

Funding

This work was supported by the Groupe Hospitalier Paris Saint‑Joseph.

Author information

Authors and Affiliations

  1. Medical and Surgical Intensive Care Department, Paris Saint Joseph Hospital, Paris, France

    Charlène Lefèvre, Théo Funck-Brentano, Alexia Plocque, Marc Tran & Francois Philippart

  2. Department of Clinical Research, Paris Saint Joseph Hospital, Paris, France

    Marine Cachanado, Maëlle Youinou, Audrey Fels & Gilles Chatellier

  3. Medical Intensive Care Department, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France

    Frédéric Pène

  4. Cochin Institute, INSERM U1016, CNRS UMR8104 Paris Cité , University, Paris, France

    Frédéric Pène

  5. Department of Respiratory and Intensive Care Medicine, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

    Laurent Savale & David Montani

  6. INSERM UMR_S 999, Marie Lannelongue Hospital, Le Plessis-Robinson, France

    Laurent Savale & David Montani

  7. Department of Internal Medicine, Groupe Hospitalier Paris Saint Joseph, Paris, France

    Olivier Voisin

  8. Department of Pneumology-Allergology-Thoracic Oncology, Paris Saint Joseph Hospital, Paris, France

    Flore Bintein

  9. Department of Anesthesiology, Intensive Care and Perioperative Medicine, Assistance Publique Hôpitaux de Paris, Paris Saclay University, 78 Rue du Général Leclerc, 94275, Le Kremlin-Bicêtre Cedex, France

    Lucille Wildenberg & Jacques Duranteau

  10. Department of Anaesthesia and Intensive Care, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Axel Philippe & Christophe Baillard

  11. Intensive Care Unit, Versailles Hospital, Versailles, France

    Stéphane Legriel

  12. University Paris Saclay UVSQ, INSERM, CESP, University Paris Saclay, Villejuif, France

    Stéphane Legriel

  13. Department of Respiratory and Intensive Care Medicine, Assistance Publique - Hopitaux de Paris, Hôpital Cochin, Paris, Île-de-France, France

    Nicolas Roche

  14. Respiratory Medicine and Cystic Fibrosis National Reference Center, AP-HP, Université Paris Cité, Cochin HospitalParis, France

    Pierre-Régis Burgel

  15. UMRS 1138, Sorbonne University, Cité University, ParisParis, France

    Pierre-Régis Burgel

  16. AP-HP, Service de Internal Medicine and Clinical Immunology, Paris-Saclay University, Bicêtre Hospital, DMU 7 Endocrinology-Immunity-Inflammation-Cancer-Emergencies, Le Kremlin-Bicêtre, France

    Nicolas Noël

  17. Endotoxins, Structures and Host Response, Department of Microbiology, Institute for Integrative Biology of the Cell, UMR 9891, CNRS, CEA-Paris Saclay University, 98190, Gif-Sur-Yvette, France

    Francois Philippart

Authors
  1. Charlène Lefèvre
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  2. Théo Funck-Brentano
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Contributions

Conceptualization: CL, TFB, AP, MT, FP. Methodology: MC, AF, GC, FP. Inclusions, review and editing: CL, TFB, AP, FP, LS, DM, OV, FB, LW, AP, SL, NR, PRB, MT, NJ, CB, JD. First draft: CL, TFB, FP. Secondary statistical analysis MY.

Corresponding author

Correspondence to Francois Philippart.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was carried out in accordance with the Declaration of Helsinki and French law. The TOCSIN study was approved by our institutional review board (GERM; IRB n°00012157). Patients were informed about the study and their non-opposition to the collection and use of non-identifying data for research purposes was obtained. The processing of patient data complied with the reference methodology 004 of the French Commission Nationale de l’Informatique et des Libertés (French National Data Protection Agency).

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Prior publication: This work was submitted on MedRxiv: https://doi.org/10.1101/2025.03.04.25323313.

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Lefèvre, C., Funck-Brentano, T., Cachanado, M. et al. Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36864-w

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  • Received: 30 May 2025

  • Accepted: 16 January 2026

  • Published: 22 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36864-w

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Keywords

  • Covid-19
  • Tocilizumab
  • Nosocomial infections
  • Ventilator-associated pneumonia
  • Neutropenia
  • Mortality
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