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

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

doi:10.1177/1559325820956800

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.

Highlights

As the coronavirus disease COVID-19 has spread the globe, physicians are confronted with patients that progressively develop severe pneumonia as a consequence of an excessive inflammatory response against SARS-CoV-2
Exploring immunomodulatory treatments to mitigate the progression to acute respiratory distress syndrome (ARDS) in severe COVID-19 may prove
We present extant and newly analyzed evidence of the effectiveness of low dose radiation therapy ( Low-dose radiation therapy (LD-RT)), and propose a treatment schedule that we hope to be of benefit to severely ill COVID-19 patients in dire straits

Summary

Introduction

As the coronavirus disease COVID-19 has spread the globe, physicians are confronted with patients that progressively develop severe pneumonia as a consequence of an excessive inflammatory response against SARS-CoV-2. Rousseau reported on 176 pneumonia patients treated with LD-RT and provided a control mortality rate by using data on pneumonia cases of the same hospital.[14] Of the group receiving treatment, 5.7% died, compared to the overall hospital pneumonia mortality rate of 28%. The current COVID-19 crisis has fostered needs for more effective treatment of the most severely afflicted patients, and has generated renewed interest in the putative benefit and value of LD-RT.

Results

Conclusion