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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Datasets used/analyzed in this study are accessible upon reasonable request to the corresponding author.
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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
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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.
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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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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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DOI: https://doi.org/10.1038/s41598-026-36864-w


