Low-dose radiotherapy for treatment of Covid

Postmortem analysis in COVID-19 infected patients has shown diffuse alveolar damage with inflammatory infiltrate present. It has been suggested that COVID-19 can induce a cytokine release syndrome caused by a systemic inflammatory response. This pulmonary hyperinflammation would be associated with severe acute respiratory syndrome, which has been described as the main cause of COVID-19 mortality. Radiation therapy administered at low doses (LD-RT) has antiinflammatory properties such as lowering levels of proinflammatory cytokines, inhibiting endothelial-leukocyte interaction, and changing the polarization of macrophages. In addition, LD-RT was used for pneumonia in the first half of the 20th century with evidence suggesting potential efficacy. In this context, several institutions proposed trials to evaluate the safety and efficacy LDRT to treat COVID-19 pneumonia. We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥ 50 years-old, with bilateral lung involvement at imaging study and oxygen requirement. Patients received 1 Gy to total lungs in a single fraction. Forty-one patients were included. Three patients died <72h after LD-RT and were excluded from the analysis. Primary outcome was radiological response assessed by severity and extension scores at days 0, +3 and +7. Lung extension score on CT improved significantly (p=0.02) on day +7, however severity score was stable or slightly decreased (p=0.1). Clinically, patients improved SatO2/ FiO2 index significantly on day +3 and +7 (p<0.01). Our results are in agreement with previous data published by Ameri et al. They analyzed 9 patients treated with 0.5 or 1 Gy and found a SatO2 improvement in 63.6% of the patients 24 hours after RT, no significant differences were found between both fractionations. Hess et al compared 10 patients treated with 1.5 Gy whole-lung LD-RT with 10 control patients blindly matched by age and comorbidity, and they concluded that patients treated with LD-RT showed a significant faster recovery to room air than controls (3 days vs 12 days respectively, p=0.05). Also, LD-RT cohort trended toward superior rates of improved radiographs (P=0.12), delirium (P <.01), rate of intubation (10% vs 40%) and median time to hospital discharge (12 days vs 20 days). At our cohort with a median follow up of 95 days, 25 (66%) patients were discharged with a similar time to that reported by Hess et al, and 13 (34%) died. Less promising results were found when LD-RT was explored in critically ill patients requiring mechanical ventilation. Papachristofilou et al, randomized 22 patients to either 1 Gy whole-lung RT or sham-RT. They hypothesized that LD-RT would increase ventilator-free days (VFDs) to 10 days. The study failed to improve VFDs compared to sham-RT. LD-RT neither improved PaO2/FiO2 or overall survival at 28 days at this severe ill cohort. Moreover, although the baseline characteristics were overall similar in both groups, there was a higher proportion of patients managed with endotracheal intubation and higher rate of comorbidities in the LD-RT group. At our cohort only 5 patients (13%) were at ICU, 3 died and 2 were discharged. Regarding toxicity, no grade 3 was found in the reported studies. However, in our cohort 9 patients (23.7%) experimented grade 3-4 lymphopenia, although 8 of them had lymphopenia before treatment. Preliminary results show that LD-RT is feasible and well-tolerated treatment, with potential clinical improvement. Prospective randomized trials are needed to define the real efficacy of LD-RT.