Response to "Comments on whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial)".

To the Editor

We went through the comments put forward by Özyürek et al. [1] and firstly, we thank the authors and appreciate their interest in our manuscript [2]. First, regarding COVID-19 vaccination, most of the patient accrual happened around the time of initial phase of vaccine rollout in the country. Our Institutional scientific review committee advised against inclusion of vaccinated individuals in the clinical trial as there might be a confounding effect while reporting unforeseen adverse effects due to either the vaccine or LDRT. Therefore, none of the participants were vaccinated (partially/whole) at the time of their inclusion in the study.

Second, regarding the smoking status, Eight out of 34 participants in the LDRT arm were smokers. Two patients (75/Male, 25 pack years and 43/Male, 20 pack years) had died amongst these eight. In the control arm, five out of 17 participants were smokers. Two out of these five had died (54/Male, 18 pack years and 60/Male, 14 pack years).

Third, about the inflammatory markers response, we would like to clarify that the LDRT group, in fact had significant reduction in inflammatory biomarkers- CRP, IL-6 and Serum ferritin on comparison of their day 7 and day 14 values with the baseline. We had observed similar reduction in control group as well. Therefore, the ‘within-group’ comparisons were statistically significant. The manuscript presented a ‘between-group’ comparison that did not achieve statistical significance. Systemic inflammatory markers may be subject to variations in presence of co-existing bacterial infections as mentioned in the manuscript. The anti-inflammatory effect has translated to rapid and evident clinical improvement backed by discernible radiological resolution implying the additional therapeutic benefit with LDRT compared to pharmacological therapy alone.

Lastly, we agree that the notable difference in comorbidities between the patient groups was one of the drawbacks of the study. Age, sex and comorbidities based stratified analysis would have allowed for better interpretation of the study results. But, this would have meant longer time to recruit patients. In the face of ongoing pandemic and acute oxygen crisis in our country at that time, we felt it was better for the study results to be published as soon as possible [3].

We once again thank Özyürek et al. for raising valid and relevant scientific queries and comments on our manuscript.