Immunomodulation Through Low-Dose Radiation for Severe COVID-19: Lessons From the Past and New Developments
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
(2020) Dose-response : a publication of International Hormesis Society, volume 18, issue 3, pp. 1 - 8
(Article)
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
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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.
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Keywords: COVID-19, cytokine storm, inflammation, low-dose radiation, treatment, Public Health, Environmental and Occupational Health, Health, Toxicology and Mutagenesis, Toxicology, Chemical Health and Safety
ISSN: 1559-3258
Publisher: International Dose-Response Society
Note: Funding Information: EJC acknowledges longtime support from the US Air Force (AFOSR FA9550-19-1-0413) and ExxonMobil Foundation (S18200000000256). Dr. Giordano?s work is supported, in part, by funding from NeuroGen, BNB Corporation, Leadership Initiatives, and the Henry Jackson Foundation. The U.S. Government is authorized to reproduce and distribute for governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the author and should not be interpreted as necessarily representing policies or endorsement, either expressed or implied. Sponsors had no involvement in study design, collection, analysis, interpretation, writing and decision to and where to submit for publication consideration. The author(s) received no financial support for the research, authorship, and/or publication of this article. Funding Information: EJC acknowledges longtime support from the US Air Force (AFOSR FA9550-19-1-0413) and ExxonMobil Foundation (S18200000000256). Dr. Giordano’s work is supported, in part, by funding from NeuroGen, BNB Corporation, Leadership Initiatives, and the Henry Jackson Foundation. The U.S. Government is authorized to reproduce and distribute for governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the author and should not be interpreted as necessarily representing policies or endorsement, either expressed or implied. Sponsors had no involvement in study design, collection, analysis, interpretation, writing and decision to and where to submit for publication consideration. Publisher Copyright: © The Author(s) 2020.
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