Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia

  1. Clayton B. Hess
  2. Zachary S. Buchwald
  3. William Stokes
  4. Tahseen H. Nasti
  5. Jeffrey M. Switchenko
  6. Brent D. Weinberg
  7. Nadine Rouphael
  8. James P. Steinberg
  9. Karen D. Godette
  10. David Murphy
  11. Rafi Ahmed
  12. Walter J. Curran
  13. Mohammad K. Khan

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Abstract

Background

Safety of whole-lung low-dose radiation therapy (LD-RT) for COVID-19 pneumonia has been established in two phase I trials. By focally dampening pulmonary cytokine hyperactivation, LD-RT may improve outcomes in hospitalized and oxygen-dependent COVID-19 patients.

Methods

Patients with COVID-19 pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or at least until hospital discharge, and compared to an age- and comorbidity-matched control cohort. COVID-19-positive patients eligible for this protocol were hospitalized, had radiographic consolidations, and required supplemental oxygen. Efficacy endpoints were time to clinical recovery, radiographic improvement, and serologic responses.

Results

Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten matched control patients, of whom six received COVID-directed therapy. Median time to clinical recovery was 12 days for the control cohort vs 3 days for LD-RT (HR 2.9, p=0.05). Median time to hospital discharge (20 and 12 days, p=0.19), and intubation rates (40% and 10%, p=0.12) were shorter for the LD-RT cohort. The LD-RT cohort had faster radiographic improvement (p=0.03), even among patients with high COVID burden. Serologic recovery in specific hematologic, cardiac, hepatic, clotting, and inflammatory markers occurred more rapidly following LD-RT than among matched controls.

Conclusions

Strong efficacy signals, including a 3-fold risk reduction in time to clinical improvement, were observed following LD-RT compared to matched patients receiving COVID-directed therapy for COVID-19 pneumonia. Given the global availability of radiation accelerators, ongoing international efforts to investigate the optimal role of LD-RT in COVID-19 pneumonia are justified.

Clinical Trial Registration

NCT04366791.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.11.20147793: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The research protocol was approved by the Emory University Institutional Review Board.
    Consent: All participants gave written informed consent prior to any study procedures.
    Randomizationnot detected.
    BlindingStudy investigators were blinded to the selection and outcomes of control patients, who were matched by age and comorbidity burden.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Limitations to this study includes the non-randomized approach, small patient numbers, non-contemporaneous controls, limited imaging and serological studies in the control cohort beyond 7 days, and lack of detailed viral load evaluations in the LD-RT and control cohorts. Future work with LD-RT will include detailed CD-8 T-cell activation studies, CD-4 T cell activation, changes in B-cell profiles, antibody formation, and neutralization tests. This further immunological analysis will provide additional insights regarding the role of LD-RT to not only improve clinical outcomes, but perhaps aid viral clearance.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04366791SuspendedRadiation Eliminates Storming Cytokines and Unchecked Edema …
    NCT04280705CompletedAdaptive COVID-19 Treatment Trial (ACTT)
    NCT04433949RecruitingBest Supportive Care With or Without Low Dose Whole Lung Rad…

    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

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  2. Version published to 10.1101/2020.07.11.20147793v1 on medRxiv