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

• Published in: Dose-Response Vol. 18; no. 3; p. 1559325820956800
• Main Authors: Hanekamp, Yannic N., Giordano, James, Hanekamp, Jaap C., Khan, Mohammad K., Limper, Maarten, Venema, Constantijn S., Vergunst, Samuel D., Verhoeff, Joost J. C., Calabrese, Edward J.
• Format: Book Review Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2020; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Clinical trials; Coronaviruses; COVID-19; Pneumonia; Review; COVID-19; low-dose radiation; treatment; cytokine storm; inflammation
• ISSN: 1559-3258; 1559-3258
• DOI: 10.1177/1559325820956800

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.