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

Little, Mark P; Zhang, Wei; Hamada, Nobuyuki

Currently, there are at least 14 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia in seven countries. One of the underlying assumptions is that irradiation at the level of about 1 Gy is effective at ameliorating viral pneumonia. Its rationale, however, relies on early human case studies or animal studies mostly obtained in the pre-biotic era, where rigorous statistical analyses were not performed. It therefore remains unclear whether those early data would support such assumptions. With state-of-the-art statistical models, we re-analyzed eleven radiobiological animal datasets (generally dating from the 1920s to early 1970s) in which animals received moderate doses of radiation before or after bacterial or viral inoculation. A number of different model systems (guinea pigs, dogs, cats, mice) and types of challenging infection, both bacterial and viral, are considered. For post-inoculation radiation exposure (which is more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with one study (of six) showing a significant increase in risk associated with radiation exposure, another showing a significant decrease in risk associated with radiation exposure, and all other results being non-significant. For pre-inoculation exposure the results are also heterogeneous, with four (of six) datasets showing significant increase in risk associated with radiation exposure and the other two showing a significant decrease in risk. Collectively, these data do not suggest that there are strong modifying effects of radiation exposure after inoculation. Although there are stronger indications of modifications of risk by radiation exposure before inoculation, the inconsistency of direction of effect makes this body of data difficult to interpret.