Pneumonia after bacterial or viral infection preceded or followed by radiation exposure -- a reanalysis of older radiobiological data and implications for low dose radiotherapy for COVID-19 pneumonia

TL;DR

This study reanalyzed old radiobiological animal data to evaluate the effects of low dose radiation on pneumonia, finding inconsistent results and questioning the assumption that radiation can effectively treat COVID-19 pneumonia.

Contribution

It provides a systematic reanalysis of historical animal data using modern statistical models, challenging the basis for low dose radiotherapy in COVID-19 treatment.

Findings

Heterogeneous effects of radiation on mortality in animal studies

No clear evidence supporting reduction in morbidity or mortality

Caution advised in interpreting old radiobiological data

Abstract

Currently, there are 14 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia. An underlying assumption is that irradiation of about 1 Gy is effective at ameliorating viral pneumonia. Its rationale, however, relies on early human case series or animal studies mostly obtained in the pre-antibiotic era, where rigorous statistical analyses were not performed. It therefore remains unclear whether those early data support such assumptions. With standard statistical survival models, and based on a systematic literature review, we re-analyzed 14 radiobiological animal datasets in which animals received mostly fractionated doses of radiation before or after bacterial/viral inoculation, and assessing various health endpoints (mortality, pneumonia morbidity). In most datasets absorbed doses did not exceed 7 Gy. Various different model systems and types of challenging infection are considered. For 7 studies that evaluated post-inoculation radiation exposure (more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with 2 studies showing a significant increase (p<0.001) and another showing a significant decrease (p<0.001) in mortality associated with radiation exposure. For pre-inoculation exposure the results are also heterogeneous, with 6 datasets showing a significant increase (p<0.01) in mortality risk associated with radiation exposure and the other 2 showing a significant decrease (p<0.05) in mortality risk. Collectively, these data do not provide clear support for reductions in morbidity or mortality associated with post-infection radiation exposure. For pre-infection radiation exposure the inconsistency of direction of effect makes this body of data difficult to interpret. Nevertheless, one must be cautious about adducing evidence from the published reports of these old animal datasets.