Whole-lung low-dose radiation therapy (LD-RT) for non-intubated oxygen-dependent patients with COVID-19-related pneumonia receiving dexamethasone and/or remdesevir

Clayton B Hess, Tony Y Eng, Tahseen H Nasti, Vishal R Dhere, Troy J Kleber, Jeffrey M Switchenko, Brent D Weinberg, Nadine Rouphael, Sibo Tian, Soumon Rudra, Luisa S Taverna, Alvaro Perez Daisson, Rafi Ahmed, Mohammad K Khan, Clayton B Hess, Tony Y Eng, Tahseen H Nasti, Vishal R Dhere, Troy J Kleber, Jeffrey M Switchenko, Brent D Weinberg, Nadine Rouphael, Sibo Tian, Soumon Rudra, Luisa S Taverna, Alvaro Perez Daisson, Rafi Ahmed, Mohammad K Khan

Abstract

Background: Low-dose radiotherapy (LD-RT) has produced anti-inflammatory effects in both animal models and early human trials of COVID-19-related pneumonia. The role of whole-lung LD-RT within existing treatment paradigms merits further study.

Methods: A phase II prospective trial studied the addition of LD-RT to standard drug treatments. Hospitalized and oxygen-dependent patients receiving dexamethasone and/or remdesevir were treated with 1.5 Gy whole-lung LD-RT and compared to a blindly-matched contemporaneous control cohort.

Results: Of 40 patients evaluated, 20 received drug therapy combined with whole-lung LD-RT and 20 without LD-RT. Intubation rates were 14% with LD-RT compared to 32% without (p = 0.09). Intubation-free survival was 77% vs. 68% (p = 0.17). Biomarkers of inflammation (C-reactive protein, p = 0.02) and cardiac injury (creatine kinase, p < 0.01) declined following LD-RT compared to controls. Mean time febrile was 1.4 vs 3.3 days, respectively (p = 0.14). Significant differences in clinical recovery (7.5 vs. 7 days, p = 0.37) and radiographic improvement (p = 0.72) were not detected. On subset analysis, CRP decline following LD-RT was predictive of recovery without intubation compared to controls (0% vs. 31%, p = 0.04), freedom from prolonged hospitalizations (21+ days) (0% vs. 31%, p = 0.04), and decline in oxygenation burden (56% reduction, p = 0.06). CRP decline following 1st drug therapy was not similarly predictive of outcome in controls (p = 0.36).

Conclusions: Adding LD-RT to standard drug treatments reduced biomarkers of inflammation and cardiac injury in COVID-19 patients and may have reduced intubation. Durable CRP decline following LD-RT predicted especially favorable recovery, freedom from intubation, reduction in prolonged hospitalization, and reduced oxygenation burden. A confirmatory randomized trial is now ongoing.

Clinical trial registration: NCT04366791.

Keywords: COVID-19; Low-dose radiation; Pneumonia.

Conflict of interest statement

Declaration of Competing Interest First (CBH) and last (MKK) authors disclose a provisional patent and relationship with CureRays, Inc. No other relevant disclosures for remaining authors.

Copyright © 2021 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram.
Fig. 2
Fig. 2
Freedom from intubation for the entire LD-RT cohort vs. matched controls.
Fig. 3a
Fig. 3a
Time to clinical recovery for LD-RT responders vs. controls.
Fig. 3b
Fig. 3b
Time from admission to clinical recovery for LD-RT responders vs. controls.
Fig. 3c
Fig. 3c
Total hospital duration for LD-RT responders vs. controls.
Fig. 3d
Fig. 3d
Intubation-free survival for LD-RT responders vs. controls.
Fig. 4
Fig. 4
ARDS X-ray scale scores by hospital day.
Fig. 5
Fig. 5
Radiographic changes after low-dose whole-lung radiotherapy (LD-RT).
Fig. 6
Fig. 6
Serologic median and interquartile ranges after low-dose whole-lung radiation therapy with concurrent dexamethasone and/or remdesevir.

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Source: PubMed

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