Clinical evaluation of IFN beta1b in COVID-19 pneumonia: a retrospective study

  1. Miriam Estébanez
  2. German Ramírez-Olivencia
  3. Tatiana Mata
  4. David Martí
  5. Carlos Gutierrez
  6. Begoña de Dios
  7. María Dolores Herrero
  8. Ana Roel
  9. Yolanda Martínez
  10. Alejandro Aguirre
  11. Francisco Alcántara-Nicolás
  12. Pablo Fernández-González
  13. Elena López
  14. Lucía Elena Ballester
  15. María Mateo-Maestre
  16. Sergio Campos
  17. María Jesús Sánchez-Carrillo
  18. Antonio Fe
  19. Francisco Javier Membrillo de Novales
  20. COVID 19 CENTRAL DEFENSE HOSPITAL “GÓMEZ ULLA” TEAM

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Abstract

Background

COVID-19 pneumonia is associated with significant mortality and has no approved antiviral therapy. Interferon beta1 has shown in vitro studies a potent inhibition of SARS-CoV and MERS-CoV. In an in vitro study, SARS-CoV-2 had more sensitivity to IFN-I pretreatment that SARS-CoV. A combination of IFN beta1b administered subcutaneously with other antiviral treatments has been recommended in several guidelines. However, clinical trial results for the treatment of COVID-19 are pending. We aimed to assess the efficiency of IFN beta1b in COVID19 comparing the in-hospital mortality between patients who received IFN beta1b and patients did not receive.

Methods

In this retrospective cohort study, we included hospitalized adults with COVID-19 between February 23th and April 4th, 2020, at the Central Defense Hospital (Madrid, Spain). Subcutaneous interferon beta-1b was recommended in moderate-severe pneumonia. The primary endpoint was in-hospital mortality. Univariate and multivariate analysis was performed to identify variables associated with in-hospital mortality.

Findings

We analyzed 256 patients (106 patients in interferon group and 150 patients in control group). At admission, patients who did not receive interferon beta1b presented a greater number of comorbidities. The overall mortality rate was 24.6% (63/256). Twenty-two patients (20.8%) in the interferon group died and 41 (27.3%) in the control group (p=0.229). In the multivariate analysis, the predictors of in-hospital mortality were age, severity of clinical picture at admission and hydroxychloroquine treatment.

Interpretation

In hospitalized patients with COVID-19, interferon beta1b treatment was not associated to decrease in-hospital mortality. Further assessment of the earlier administration of this drug in randomized trials is recommended.

Funding

none.

RESEARCH IN CONTEXT

Evidence before this study

We searched Pubmed on April 27 th , 2020, for articles evaluating the efficacy of interferon beta in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the terms: “interferon beta and (COVID-19 or SARS-CoV-2)”. We only found 5 articles. Of them, there was only one original article in English, which was a descriptive study of a case series with solid organ transplant from Spain.

Added value of this study

This is the first article that reports the efficacy of interferon beta1b in the treatment of patients with COVID-19. We compared the in-hospital mortality between patients who received interferon beta1b and patients who did not. Patients in both groups received other drugs with a potential antiviral and immunomodulatory effect. There was no significant difference in in-hospital mortality between both groups.

Implications of all the available evidence

In our retrospective cohort, treatment with interferon beta1b had not impact on in-hospital survival, however it would be of clinical interest to evaluate the effect of early administration of this drug in the control of SARS-CoV-2 infection in larger randomized clinical trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.15.20084293: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethics approvals: From beginning of COVID-19 epidemic, eligible hospitalized patients were offered treatment with subcutaneous interferon beta1b after informed verbal consent was obtained from the patients themselves or their closest relative.
    IRB: The research protocol was approved by the Ethics Committee on Clinical Investigation of the Ministry of Defense of Spain (code 25/20).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis was performed using SPSS version 25 statistical package.
    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:
    Our study has the limitations of a retrospective study, selection and unmeasured confounding bias cannot be completely excluded. It would have been ideal to have had microbiological confirmation of all the patients, but since this study had been carried out in the worst phase of the epidemic in our country, at specific times and due to lack of tests, microbiological confirmation was not necessary in cases of high clinical and radiological suspicion without any other alternative cause. Furthermore, we cannot evaluate differences between the two groups in terms of virus elimination, as there was no RT-PCR monitoring for all patients. This study is, to the best our knowledge, the first clinical study that evaluates the effectiveness of the interferon beta1b in SARS-CoV-2 infection. Conclusion: In our retrospective cohort, the interferon beta1b treatment had no significant impact on in-hospital survival. We consider that it would be of interest to explore the efficacy of the early administration of this drug in controlled clinical trials, with a larger sample size.

    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 10.1101/2020.05.15.20084293v2 on medRxiv
  3. Version published to 10.1101/2020.05.15.20084293v1 on medRxiv