We conducted a systematic review and meta-analysis to estimate the SR for COVID-19 patients treated with LDRT. Our opinion is that the lack of a good systematic review and meta-analysis has led to unjustified radiation exposure of COVID-19 patients worldwide.
LDRT for COVID-19 was supplemented with radiotherapy that is easily accessible worldwide (Sterne et al. 2011; Bhandari et al. 2020; Zhang et al. 2020; Papachristofilou et al. 2021; Ameri et al. 2021b). Several studies have shown that LDRT can control pneumonia (Ameri et al. 2020, 2021b; Khan et al. 2020; Hess et al. 2020; Moreno-Olmedo et al. 2021b; Papachristofilou et al. 2021; Sanmamed et al. 2021; Sharma et al. 2021; Arenas et al. 2021). At 0.5 and 1 Gy radiation doses, LDRT can significantly affect lung macrophages. The exposure of human lung macrophages to LDR can decrease IFNγ production and increase IL-10 secretion(Rödel et al. 2007). As a result of LDRT, human lung macrophages can produce more IL-10(Rödel et al. 2007). In contrast, LDRT decreases the percentage of human lung macrophages that produce IL-6. Regardless of sex and age, doses less than 1 Gy can provide an acceptable lifetime attributable risk (LAR) of radiation-induced cancer (Trott and Kamprad 2006; Shuryak et al. 2021).
According to a recent paper (Lumniczky et al. 2021b), doses up to 1 Gy have anti-inflammatory effects, while doses above 1 Gy cause pro-inflammatory effects.
LDRT with doses up to 250 mGy was first proposed by Ghadimi-Moghadam(Ghadimi-Moghadam et al. 2020) in March 2020. Eventually, researchers worldwide increased radiation doses in competition with one another. The Emory University Hospital (Hess et al. 2021) used 1.5 Gy, while Ameri et al. used 0.5 Gy and 1.0 Gy (Ameri et al. 2020, 2021a).
A recent randomized trial involving 22 elderly COVID-19 patients with pneumonia and mechanical ventilation showed that whole-lung LDRT was ineffective in improving clinical outcomes (Papachristofilou et al. 2021).
Consequently, the doses used in the clinical trials conducted by Emory University Hospital may have been unjustified (Hess et al. 2020). LDRT might not be effective in Switzerland because of the relatively high dose used (Papachristofilou et al. 2021). Furthermore, this point clarifies why Ameri et al. finally admitted that 0.5 Gy was more effective than 1.0 Gy in their trial.
The use of doses less than 0.5 Gy not only increases the therapeutic effects of LDRT and maintains the risks at an acceptable level but also decreases the cancer risk to a reasonable level. In their trials, Ameri et al., Papachristofilou et al., and Sanmamed et al. used doses of 1 Gy.
Except for one study, all clinical, radiological, and survival outcomes improved. The study showed that whole-lung radiation at doses of 0.5–1.5 Gy was beneficial to patients with COVID-19-associated pneumonia who were oxygen-dependent. The results of our study did not find any evidence of acute radiation toxicity.
Our meta-analysis found an association between LDRT and a higher chance of survival among COVID-19 patients. The calculated survival rate was 0.59 (95% CI, 0.44:0.75). Thus, we can demonstrate that LDRT significantly impacts the recovery of severe COVID-19 patients. Moreover, we found that a dose above 1 increases mortality risk.
This study has several limitations, which should be considered when interpreting its results. First, the study has a small sample size, which may result in underpowered results. Second, the interval delimitations are not precise and uniform due to a lack of information in the included study. Finally, the quality of different studies was different, which could cause bias.