Whole-Lung Low-Dose Radiation Therapy (LD-RT) for Non-Intubated Oxygen-Dependent Patients with COVID-19-Related Pneumonia Receiving Dexamethasone and/or Remdesevir

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

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. Funding: None