Human medical trials have begun on severely ill COVID-19 patients using low-doses of radiation. The first results on a very small group were published this week in a non-peer-reviewed journal that exists to get critical results out quickly to the scientific and medical community.
The medical team at Emory University Hospital led by Dr. Mohammad Khan (on the right; Dr. Clayton ... [+]
The results were quite extraordinary.
Researchers at Emory University Hospital, led by Dr. Mohammad Khan, Associate Professor of Radiation Oncology, treated ten COVID-19 patients with severe pneumonia who were requiring supplemental oxygen and whose health was visibly deteriorating. Their median age was 78 with a range from 43 to 104, in a mix of female, male, African-American and Caucasian.
These patients were given a single low-dose of radiation (1.5 Gy) to both lungs, delivered by a front and back beam configuration. Patients were in an out of the Radiotherapy Department in 10 to 15 minutes.
Within 24 hours, nine of the patients showed rapid improvement in oxygenation and mental status (more awake, alert and talkative) and were being discharged from the hospital 12 days later. Blood tests and repeated imaging of the lungs confirmed that the radiation was safe and effective, and did not cause adverse effects - no acute skin, pulmonary, gastrointestinal or genitourinary toxicities.
The gray (Gy) is a dose unit of ionizing radiation defined as the absorption of one joule of radiation energy per kilogram of matter. The Gy replaces the older unit of the rad, and 1 Gy = 100 Rad. I should mention that medical doses are different than environmental doses as they are not whole body, but are targeted to a specific organ or tissue. So 1.5 Gy is quite low dose for medical uses.
This treatment is critical because severe COVID-19 cases cause cytokine release syndrome, also known as a cytokine storm. Such a storm is a deadly uncontrolled systemic inflammatory response of the body’s immune system resulting from the release of great amounts of pro-inflammatory cytokines, which act as a major factor in producing acute respiratory distress syndrome, or ARDS, which is what kills.
It’s why we need ventilators and ICU beds so badly, and why this pandemic threatens to overwhelm our hospital systems.
One reason why this trial is so important, and why the success rate was so exciting, is COVID-19’s increasing fatality rates with age - 8% for patients aged 70 to 79 and 14.8% for those aged 80 and over - so showing this treatment is safe and effective for these elderly patients was vital. Mortality rates are even higher if you get hospitalized and are in the ICU, over 50%.
It’s the anti-inflammatory effects of radiation, not its antiviral action, and it’s these anti-inflammatory effects that is invaluable in helping patients with COVID-19 and that were demonstrated in this trial.
We are already completely set up for these radiation treatments at almost every hospital and cancer center - no new preparation, additional equipment, or training is needed. There is no supply chain issue with this treatment.
We could have been doing this since the pandemic began and saved tens of thousands of lives.
As discussed previously, several medical institutions are starting radiation therapies for COVID-19. The Clinicaltrials.gov website gives information on these trials, including an Italian clinical trial, a Spanish clinical trial and others that have begun and more have recently been added to the ClinicalTrials.gov website, with five of them currently recruiting patients. The countries represented are USA(2), Spain(2), Italy (1), Iran(1). These trials are also using lower doses, in the range of 0.3 to 0.7 Gy.
One trial in India, at the AIIMS facility in New Delhi, has finished and the results are similar. Also very small, Dr. D.N. Sharma gave two severely ill patients 0.7 Gy to the lungs and they are now stable and off of oxygen. Ten other patients are scheduled to be treated soon.
Dr. James Welsh at Loyola University Medical Center, and former Chairman of the Board of the American College of Radiation Oncology and Editor-in-Chief of the Journal of Radiation Oncology, is moving to begin a national trial within the next few months on this treatment using low-dose radiation to the lungs.
Welsh and colleagues from Beaumont Health, Ohio State University, Baptist Health Miami and Barrow Neurological Institute, just published an article on the basic science behind this method (see figure below from this publication, published and modified, with permission, from Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020; 27:1451– 4. © 2020 Radiation Research Society).
Potential role of low-dose radiation to combat the cytokine storm in severe pneumonia associated ... [+]
These studies indicated possible mechanisms by which low doses of radiation mitigates inflammation and facilitates healing, one being the polarization of macrophages to an anti-inflammatory or M2 phenotype. The M1 type tends to overstimulate the immune system which can lead to a cytokine storm, while the M2 type tends to suppress the overreaction of the immune system.
We kind of knew this would work because we did the same thing 70 to 80 years ago. Dr. E. J. Calabrese at the University of Massachusetts School of Public Health & Health Sciences and Dr. Gaurav Dhawan at the University of Massachusetts reviewed how X-ray therapy was used during the first half of the 20th century to successfully treat pneumonia, especially viral pneumonia like that caused by this coronavirus.
Unfortunately, 70 years of irrational and unfounded fear of low doses of radiation, even those doses that occur naturally in the environment, have prevented testing of many of these treatments. Between the discovery of penicillin and the atomic bombs used in World War II, most interest in using radiation therapy against any disease other than cancer steadily waned.
We still don’t have any established treatment for COVID-19. Remdesivir, an RNA polymerase inhibitor, has shown promise in human trials but only in shortening recovery times by a few days. As Welsh puts it, for COVID-19 patients who become severely ill, low-dose radiation would appear to be a relatively safe strategy that could be widely implemented immediately.
As the other human radiation trials move forward, it will be exciting to see their results because we need an easy, quick and safe treatment for the most dangerous virus of our time.
The longer we dawdle, the more people will die.
