Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia?

Abstract

Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1–1 Gy) or two doses (a few mGy followed by 0.1–0.25 Gy involving a putative adaptive response, or 1–1.5 Gy in two fractions 2–3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.

Keywords:

• COVID-19
• pneumonia
• low dose radiotherapy
• clinical trials
• adaptive response

Acknowledgements

The authors would like to thank Drs Mark P. Little (NCI, USA) and Lydia Zablotska (UCSF, USA) for helpful discussion. ISGlobal acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the ‘Centro de Excelencia Severo Ochoa 2019–2023’ Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. The views expressed in this paper represent collective opinions of the authors, and are not necessarily those of their professional affiliations.

Additional information

Notes on contributors

Sisko Salomaa

Sisko Salomaa, Ph.D, is Professor of radiobiology in University of Eastern Finland and Coordinator of National Radiation Safety Research Program in STUK. As part of setting up the European low dose program (MELODI), she coordinated DoReMi Network of Excellence 2010–2015. She is representative of Finland to UNSCEAR and a member of ICRP C1.

Simon D. Bouffler

Simon D. Bouffler, Ph.D, leads the Radiation Effects Department at Public Health England. He is involved in several European research initiatives and is currently Chair of the MELODI Strategic Research Agenda working group. He leads the UK delegation to UNSCEAR and is a Main Commission member of ICRP.

Michael J. Atkinson

Michael J. Atkinson, Ph.D, is Professor of Radiation Biology at the Medical Faculty of the Technical University of Munich, Director of the Institute of Radiation Biology at the Helmholtz Zentrum München, and a member of the Federal Radiation Protection Commission in Germany.

Elisabeth Cardis

Elisabeth Cardis, Ph.D, is Research Professor in Radiation Epidemiology and Head of the Radiation Program at the Barcelona Institute for Global Health (ISGlobal) and member of the Executive Board of MELODI. Before moving to Barcelona in 2008, she created and led the Radiation Group at the WHO International Agency for Research on Cancer IARC in Lyon for nearly 20 years.

Nobuyuki Hamada

Nobuyuki Hamada, RT, Ph.D, is Senior Research Scientist at CRIEPI Radiation Safety Research Center and Visiting Professor at Hiroshima University Research Institute for Radiation Biology and Medicine. He serves on ICRP Task Groups 102 and 111, NCRP PAC 1, and IRPA Phase 3 Task Group on the implementation of the eye lens dose limits. He has published >120 papers in peer reviewed international journals.