<strong>Low-dose Whole-lung Irradiation for COVID-19 Pneumonia: What is the Optimal Dose? Final Results of a Pilot Study</strong>

Abstract

Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO2, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO2 upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO2 &amp;ge;93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO2. Five patients were discharged (median 6th day, range 2nd-14th day), and four patients died (median 7th day, range 3rd-10th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.

Nrf2 activation putatively mediates clinical benefits of low-dose radiotherapy in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS): Novel mechanistic considerations

“…The findings presented support recent demonstrations of positive clinical responses to LDRT in COVID-19 pneumonia patients [6] , [7] , [8] , [9] , [10] , [11] , [12] . However, animal studies also provide support for the effectiveness of Nrf2 in protecting various tissues from pro-inflammatory challenges.…”

In Reply to Bevelacqua et al

“…] cite the Iranian study, and declare that their concept "clearly explains why Ameri et al concluded that 0.5 Gy was more effective than 1.0 Gy". This was not a conclusion of the study's authors, who address important limitations in their paper [4]. We cannot exclude that a different outcome would have been observed in our study with use of a lower radiation dose.…”

“…Our trial was borne out of a clinical need, and we chose a randomized double-blind design to reduce any potential bias. The availability of prospective controls is the crucial difference between our study and earlier reports [4,7,8], a difference which [XXX-et-al. ] unfortunately did not consider as a source of discrepancy between results.…”

Jet fans in the underground car parking areas and virus transmission

“… 2 Studies have reported that SARS-CoV-2 spreads mainly through respiratory droplets and aerosols. 3–8 These respiratory droplets can be exhaled during coughing, sneezing, or even talking. 9 …”