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

• Authors: Yannic N. Hanekamp, University of Groningen; James Giordano, Georgetown University; Jaap C. Hanekamp, University College Roosevelt; Mohammad Khan, Emory University; Maarten Limper, Utrecht University; Constantijn S. Venema, University of Groningen; Samuel D. Vergunst, University of Groningen; Joost J. C. Verhoeff, Utrecht University; Edward J. Calabrese, University of Massachusetts
• Journal Title: DOSE-RESPONSE
• Volume: Volume 18, Number 3
• Publisher: SAGE PUBLICATIONS INC | 2020-07-01, Pages 1559325820956800-1559325820956800
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1177/1559325820956800
• Subjects: Health Sciences, Pharmacology; Health Sciences, Toxicology; Biology, Virology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology; COVID-19; low-dose radiation; inflammation; treatment; cytokine storm; X-RAYS; CYTOKINE STORM; IRRADIATION; RADIOTHERAPY; MECHANISMS; ADHESION; CELLS

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.