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

Little, Mark P.; Zhang, Wei; van Dusen, Roy; Hamada, Nobuyuki

Purpose Currently, there are about 15 ongoing clinical studies on low dose radiotherapy (LDRT) for COVID-19 pneumonia. One of the underlying assumptions is that irradiation of 0.5–1.5 Gy is effective at ameliorating viral pneumonia. We aimed to reanalyze all available experimental radiobiological data to assess evidence for such amelioration. Methods and Materials With standard statistical survival models, and based on a systematic literature review, we re-analyzed thirteen radiobiological animal datasets published in 1937-1973 in which animals (guinea pigs/dogs/cats/rats/mice) received 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. Results For six studies evaluating post-inoculation radiation exposure (more relevant to LDRT for COVID-19 pneumonia) the results are heterogeneous, with one study showing a significant increase (p<0.001) and another showing a significant decrease (p<0.001) in mortality associated with radiation exposure. Among the remaining four studies, mortality risk was non-significantly increased in two studies and non-significantly decreased in two others (p>0.05). For pre-inoculation exposure the results are also heterogeneous, with six (of eight) datasets showing a significant increase (p<0.01) in mortality risk associated with radiation exposure and the other two showing a significant decrease (p<0.05) in mortality or pneumonitis morbidity risk. Conclusions These data do not provide support for reductions in morbidity or mortality associated with post-infection radiation exposure. For pre-infection radiation exposure the inconsistency of direction of effect is difficult to interpret. One must be cautious about adducing evidence from such published reports of old animal datasets.