ABSTRACT
Introduction: Individuals with advanced age and comorbidities face risk of death from COVID-19, especially onceventilator-dependent, precipitated by an immune cytokine storm in the lungs. Lymphocytes, a mediator of cytokinestorms, are exquisitely sensitive to ionizing radiation. Low doses of radiation therapy (LD-RT) were used to treatinfectious processes during the first half of the 20th century, including pneumonia. It is conceivable that focalimmunosuppression with LD-RT may reduce pulmonary inflammation associated with COVID-19 pneumonia. Methods: The Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-day Treatment for COVID-19 (RESCUE 1-19) trial explores safety and efficacy of single-fraction, low-dose, whole-lung radiation forhospitalized, oxygen-dependent patients with COVID-19 pneumonia (Clinical Trial NCT04366791 ). Patients had tobe hospitalized with a positive COVID-19 nasopharyngeal swab, have radiographic pneumonic consolidations, require oxygen supplementation, and be clinically deteriorating (i.e., mentation, oxygenation, dyspnea). Patientsreceived a single-fraction dose of 1.5 Gy to the bilateral lungs. The primary endpoint was safety, measured by apreplanned stopping rule. We utilized an established clinical scale to define clinical recovery, the Glasgow ComaScale (GCS), an established radiographic ARDS scale, and 27 serologic biomarkers. Results: Between April 23-28, 2020, nine candidates were evaluated. Of these, one died before enrollment, one didnot meet severity criteria, and seven enrolled. Of these, two were intubated before LD-RT (one died), and fivereceived LD-RT. Median age was 90 (range 64-94). Four had been admitted from nursing homes with COVID-19outbreaks. Comorbidity burden was high. Four were African American and one was Caucasian. Four were female.Median oxygen requirement at the time of LD-RT was 3 L/min (range 1.5-6). Median duration of prehospitalizationsymptoms was 4 days (range 1-7). LD-RT was delivered on median hospital day 5 (range 2-8). Three patientsreceived azithromycin prior to enrollment. During a 14-day observation period, no patients experienced acutetoxicity. Four patients (80%) clinically recovered, 3 within 24 hours, without evidence of COVID symptomexacerbation. Mean time to recovery was 35 hours. Median GCS rose from 10 (range 9-15) to 14 (range 13-15) athour 24. Serial x-rays showed improved or stable disease in 4/5 patients. At day 7, 4/5 patients had 85-92% of allbiomarkers either improve or remain normal. At day 14, all patients were alive, 3 had returned to their nursinghomes (mean time to discharge 12 days), and a 4th was pending discharge. Conclusion: Five hospitalized, oxygen-dependent, and clinically deteriorating patients received low-dose, whole-lung radiation and experienced no acute toxicities. 80% returned to room air at a median time of 1.5 days. Noworsening of the cytokine storm was observed in 4 of 5 patients. Low-dose lung radiation appears safe and meritsfurther evaluation.