Low‐dose whole‐lung radiation for COVID‐19 pneumonia: Planned day 7 interim analysis of a registered clinical trial

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Abstract

Individuals of advanced age with comorbidities face a higher risk of death from coronavirus disease 2019 (COVID‐19), especially once they are ventilator‐dependent. Respiratory decline in patients with COVID‐19 is precipitated by a lung‐mediated aberrant immune cytokine storm. Low‐dose lung radiation was used to treat pneumonia in the pre‐antibiotic era. Radiation immunomodulatory effects may improve outcomes for select patients with COVID‐19.

Methods

A single‐institution trial evaluating the safety and efficacy of single‐fraction, low‐dose whole‐lung radiation for patients with COVID‐19 pneumonia is being performed for the first time. This report describes outcomes of a planned day 7 interim analysis. Eligible patients were hospitalized, had radiographic consolidation, required supplemental oxygen, and were clinically deteriorating.

Results

Of 9 patients screened, 5 were treated with whole‐lung radiation on April 24 until April 28 2020, and they were followed for a minimum of 7 days. The median age was 90 years (range, 64‐94 years), and 4 were nursing home residents with multiple comorbidities. Within 24 hours of radiation, 3 patients (60%) were weaned from supplemental oxygen to ambient air, 4 (80%) exhibited radiographic improvement, and the median Glasgow Coma Scale score improved from 10 to 14. A fourth patient (80% overall recovery) was weaned from oxygen at hour 96. The mean time to clinical recovery was 35 hours. There were no acute toxicities.

Conclusions

In a pilot trial of 5 oxygen‐dependent elderly patients with COVID‐19 pneumonia, low‐dose whole‐lung radiation led to rapid improvements in clinical status, encephalopathy, and radiographic consolidation without acute toxicity. Low‐dose whole‐lung radiation appears to be safe, shows early promise of efficacy, and warrants further study.

Lay Summary

  • Researchers at Emory University report preliminary safety outcomes for patients treated with low‐dose lung irradiation for coronavirus disease 2019 (COVID‐19) pneumonia.

  • Five residents of nursing or group homes were hospitalized after testing positive for COVID‐19. Each had pneumonia visible on a chest x‐ray, required supplemental oxygen, and experienced a clinical decline in mental status or in work of breathing or a prolonged or escalating supplemental oxygen requirement.

  • A single treatment of low‐dose (1.5‐Gy) radiation to both lungs was delivered over the course of 10 to 15 minutes. There was no acute toxicity attributable to radiation therapy. Within 24 hours, 4 patients had rapidly improved breathing, and they recovered to room air at an average of 1.5 days (range, 3‐96 hours). Three were discharged at a mean time of 12 days, and 1 was preparing for discharge.

  • Blood tests and repeat imaging confirm that low‐dose whole‐lung radiation treatment appears safe for COVID‐19 pneumonia. Further trials are warranted.

Article activity feed

  1. SciScore for 10.1101/2020.06.03.20116988: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The protocol was approved by the Emory University Institutional Review Board, and all human participants or their surrogate representatives gave written informed consent.
    Consent: Median Glasgow Coma Scale (GCS) score was 10 (range 9-15) at time of consent.
    Randomizationnot detected.
    Blindingnot detected.
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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

    IdentifierStatusTitle
    NCT04366791SuspendedRadiation Eliminates Storming Cytokines and Unchecked Edema …


    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.