[Low dose radiotherapy for COVID-19 pneumopathy: Biological rationale and literature review]

Abstract

The world has now been facing the coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since over a year. If most of clinical presentations are benign, fragile patients are at greater risk of developing severe or fatal lung disease. Many therapies have been explored with very low impact on mortality. In this context, Kirkby et Mackenzie have published in April 2020 a report reminding the anti-inflammatory properties of low-dose radiotherapy (delivering less than 1Gy) and its use in the treatment of viral and bacterial pneumopathies before antibiotics era. Large in vivo and in vitro data have demonstrated the biological rationale and anti-inflammatory activity of low-dose radiotherapy in many pathologies. Over the past year, three phase I/II clinical trials have been published, as well as one randomized controlled trial, reporting the feasibility and the clinical and biological improvement of a 0.5 to 1Gy treatment dose to the entire lung. 13 other studies, including a randomized phase III trial, are currently ongoing worldwide. These studies may provide data in the effect of low-dose radiotherapy in the treatment of SARS-CoV-2 pneumonia. This article explains biological rationale of low-dose radiotherapy, and reports already published or ongoing studies on low-dose radiotherapy for SARS-CoV-2 pneumonia.

Keywords: COVID-19; Covid-19; Faible dose; Low dose; Radiobiologie; Radiobiology; Radiotherapy; Radiothérapie; SARS-CoV-2.

Fig. 1

Physiopathologie de la pneumonie coronavirus disease 2019 (covid-19) et réponse biologique à la radiothérapie. A : Au cours d’une infection sévère à severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), la production insuffisante d’interféron de type I mène à la multiplication du virus à l’origine de l’orage cytokinique et de l’afflux de cellules immunitaires dans les alvéoles pulmonaires. Cette cascade provoque des lésions pulmonaires et un œdème entravant les échanges gazeux ; B : La radiothérapie de faible dose dans les poumons en cours d’infection à SARS-Cov2 limite l’inflammation en induisant l’apoptose des leucocytes et diminue leur arrivée dans le tissu interstitiel via la diminution des molécules d’adhésion endothéliales. Elle permet la polarisation des macrophages vers le phénotype M2 augmentant ainsi la production de cytokines anti-inflammatoires. LcT : lymphocyte T ; INF : interféron ; IL : interleukine ; TNFa : tumour necrosis factor alpha ; TGFb : transforming growth factor beta.