Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study

  1. Victor Carvalho
  2. Ricardo Turon
  3. Bruno Gonçalves
  4. Victor Fraga Ceotto
  5. Pedro Kurtz
  6. Cássia Righy

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Abstract

Objectives

Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU.

Design

Patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls.

Setting

COVID-19 severe disease

Patients

Patients with severe COVID-19 disease admitted in the ICU.

Interventions

Tocilizumab 400 mg IV two doses. Standard and intensive medical care as per institutional clinical protocol.

Measures and Main Results

Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls.

Conclusion

Tocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease

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  1. ScreenIT

    SciScore for 10.1101/2020.07.13.20149328: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study protocol was approved by the National Ethics Committee (4.059.207), who waived the need for informed consent.
    Consent: The study protocol was approved by the National Ethics Committee (4.059.207), who waived the need for informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableExclusion criteria: Patients with primary or secondary immunodeficiency, using immunosuppressive drugs, pregnant women, those without respiratory symptoms and in palliative care.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using IBM SPSS Statistics version 23.0 (Chicago, IL, USA) and Prism (GraphPad, San Diego, CA, USA)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, our study has some limitations. Corticosteroid use was not balanced between groups, limiting the determination of the real benefit in oxygenation and CRP reduction of tocilizumab in patients who used corticosteroid; the number of patients was limited; it was a single center study, neither blind nor randomized. Nevertheless, this study generates an interesting hypothesis on the safety of concomitant use of tocilizumab and corticosteroid in COVID patients. This hypothesis should be evaluated in a larger clinical trial.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.07.13.20149328v1 on medRxiv