Immunomodulation Through Low-Dose Radiation for Severe COVID-19: Lessons From the Past and New Developments

Yannic N Hanekamp; James Giordano; Jaap C Hanekamp; Mohammad K Khan; Maarten Limper; Constantijn S Venema; Samuel D Vergunst; Joost J C Verhoeff; Edward J Calabrese

doi:10.1177/1559325820956800

Immunomodulation Through Low-Dose Radiation for Severe COVID-19: Lessons From the Past and New Developments

Dose Response. 2020 Sep 22;18(3):1559325820956800. doi: 10.1177/1559325820956800. eCollection 2020 Jul-Sep.

Authors

Yannic N Hanekamp¹, James Giordano², Jaap C Hanekamp^{3

4}, Mohammad K Khan⁵, Maarten Limper⁶, Constantijn S Venema¹, Samuel D Vergunst¹, Joost J C Verhoeff⁷, Edward J Calabrese⁴

Affiliations

¹ University Medical Centre Groningen, University of Groningen, the Netherlands.
² Departments of Neurology and Biochemistry, and Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, Washington, DC, USA.
³ University College Roosevelt, Middelburg, the Netherlands.
⁴ Department of Environmental Health Sciences, University of Massachusetts, Amherst, MA, USA.
⁵ Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁷ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Abstract

Low-dose radiation therapy (LD-RT) has historically been a successful treatment for pneumonia and is clinically established as an immunomodulating therapy for inflammatory diseases. The ongoing COVID-19 pandemic has elicited renewed scientific interest in LD-RT and multiple small clinical trials have recently corroborated the historical LD-RT findings and demonstrated preliminary efficacy and immunomodulation for the treatment of severe COVID-19 pneumonia. The present review explicates archival medical research data of LD-RT and attempts to translate this into modernized evidence, relevant for the COVID-19 crisis. Additionally, we explore the putative mechanisms of LD-RT immunomodulation, revealing specific downregulation of proinflammatory cytokines that are integral to the development of the COVID-19 cytokine storm induced hyperinflammatory state. Radiation exposure in LD-RT is minimal compared to radiotherapy dosing standards in oncology care and direct toxicity and long-term risk for secondary disease are expected to be low. The recent clinical trials investigating LD-RT for COVID-19 confirm initial treatment safety. Based on our findings we conclude that LD-RT could be an important treatment option for COVID-19 patients that are likely to progress to severity. We advocate the further use of LD-RT in carefully monitored experimental environments to validate its effectiveness, risks and mechanisms of LD-RT.

Keywords: COVID-19; cytokine storm; inflammation; low-dose radiation; treatment.

Publication types

Review