Use of a humanized anti-CD6 monoclonal antibody (itolizumab) in elderly patients with moderate COVID-19

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Abstract

Introduction

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease (COVID-19). In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2.

Methods

Based on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti-CD6 monoclonal antibody.

Results

All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented.

Discussion/Conclusion

Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome from other pathologies.

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  1. SciScore for 10.1101/2020.07.24.20153833: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The Ethics Committee for Clinical Research in the hospital and Cuban Regulatory Agency (
    Consent: All patients met the inclusion criteria described in the protocol (http://rpcec.sld.cu/trials/RPCEC00000311-Eg.) and signed the informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The analysis was performed using SPSS 25.0 software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    This study has some limitations regarding the short kinetic of IL-6 levels and the limited follow up of the patients, long-term outcomes of them are unknown. Nevertheless, it shows the effect of itolizumab associated with a reduction and controlling IL-6 serum levels. Moreover, itolizumab treated patients had a favorable clinical outcome, considering their poor prognosis associated with old age and comorbidities, including nutrition deficit. In conclusion, this study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 and suggests its possible use in patients with cytokine release syndrome from other pathologies.

    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. SciScore for 10.1101/2020.07.24.20153833: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe Ethics Committee for Clinical Research in the hospital and Cuban Regulatory Agency (Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableResults Baseline characteristics of COVID-19 elderly patients The median age was 79 years (64 to 100 years old); 63.2% were female and 68.4% were white skin.

    Table 2: Resources

    Antibodies
    SentencesResources
    Manuscript Title: Use of a humanized anti-CD6 monoclonal antibody (itolizumab) in elderly patients with moderate COVID-19 Materials and Methods Patients Nineteen patients confirmed as SARS-CoV-2 positive by real-time transcriptase polymerase chain reaction (RT-PCR), admitted from the Cuban’s nursing home, were enrolled in an open, multicenter expanded access clinical trial (RPCEC00000311(VICTORIA)) to be treated with the humanized MAb itolizumab.
    RPCEC00000311
    suggested: None
    Treatment with an anti-CD6 monoclonal antibody (itolizumab) Immediately upon confirmation of the presence of SARS-CoV-2, the patients received the established institutional COVID-19 treatment protocol [11].
    anti-CD6
    suggested: None
    Software and Algorithms
    SentencesResources
    The analysis was performed using SPSS 25.0 software.
    SPSS
    suggested: (SPSS, SCR_002865)

    Data from additional tools added to each annotation on a weekly basis.

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.