Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with COVID-19-Related Pneumonia

PURPOSE/OBJECTIVE: Phase I clinical trials have established low-dose, whole-lung radiotherapy (LD-RT) as safe for patients with COVID-19-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation. METHODS AND MATERIALS: Patients with COVID-19-related pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared to age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, SARS-CoV-2 positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or prior to drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery (TTCR), radiographic improvement, and biomarker response. RESULTS: Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median TTCR was 12 days in the control cohort compared to 3 days in the LD-RT cohort (HR 2.9, p=0.05). Median time to hospital discharge (20 versus 12 days, p=0.19) and intubation rates (40% versus 10%, p=0.12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (p=0.13). Hospital duration average was 19 versus 22.6 days (p=0.53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (p=0.69). Average days with a documented fever was 1 versus 4.3 days (p=0.12). 28-day overall survival was 90% for both cohorts. The LD-RT cohort trended towards superior rates of improved radiographs (p=0.12) and delirium (p