Back in 2013, toxicologist Edward Calabrese and a colleague at the University of Massachusetts, Amherst, were combing over a cache of century-old data on low-dose radiation therapy, hunting for evidence on the scientific idea that small doses of certain poisons might actually be beneficial.
They found small amounts of radiation were surprisingly successful in combating pneumonia. Again and again, doctors reported symptoms subsided within hours of a single X-ray.
The use of “micro-doses” of radiation as therapy for various aliments has come up before here: The Radioactive Remedy.
The current desperation for a vaccine and/or cure is leading to a reexamination of all kinds of older ideas and methods that were superseded by modern medicine.
Using radiation as medicine follows the old idea that a tiny dose of poison that would kill you can be good for you, which is remarkably similar to the modern concept of vaccinations.
At least 52,000 of the more than 135,000 deaths due to Covid-19 in the U.S. have involved pneumonia, according to federal health data.
There are at least a dozen trials worldwide testing low-dose radiation therapy, or LDRT, as a treatment for pneumonia related to Covid-19, some spurred by the same historical data Calabrese and colleagues scoured years ago.
The theory: Targeted radiation to the lungs will halt the out-of-control inflammation responsible for the devastating pneumonia that bookends the course of some Covid-19 patients.
But the revived interest in radiotherapy has sparked a debate among physicians and researchers, who are divided on whether the idea is even ready for test-driving in clinical trials.
With little known about the way LDRT works on inflamed lungs, some experts say it might exacerbate respiratory damage, while introducing the additional risk of cancer. Others say patients participating in the trials may suffer by missing out on more promising treatments.
On the other side, though, are experts who say there’s a clear and urgent need for Covid-19 treatments that work, particularly for cases that become severe. Antibiotics can help treat cases of pneumonia from bacterial infections, but not those caused by viruses.
The new wave of low-dose radiation trials are registered at academic centers and hospitals around the world, including in Italy, Spain, Iran, India, and the U.S. The studies are recruiting anywhere from five to 106 Covid-19 patients with pneumonia, and half require participants to be at least 40 years of age.
Arnab Chakravarti, chair of Ohio State’s radiation and oncology department, is spearheading two of the four LDRT trials in the U.S.
Chakravarti hypothesizes that LDRT will tamp down the unchecked inflammation that ultimately overwhelms the lungs of some Covid-19 patients. In these individuals, immune cells overreact to the virus and secrete a dangerous excess of proinflammatory cytokines, known as a “cytokine storm.”
The idea is that low-dose lung radiation has the potential to reduce this inflammatory response.”
Some experts have theorized that small amounts of radiation might flip a switch on these immune cells so that they release soothing, anti-inflammatory cytokines instead, though this is just one among many proposed mechanisms.
Beyond historical data, Chakravarti said that his hypothesis is staked in recent evidence from an interim analysis of a clinical trial at Emory testing low-dose radiation in ten patients with Covid-19. All of the first five patients, averaging 90 years of age, were alive two weeks after treatment, and researchers reported three patients were weaned off oxygen within 24 hours of receiving radiation.
The Emory researchers published updated data this month from 10 patients — including the initial five in the first study — in preprint paper, which found that LDRT was associated with a reduction in clinical recovery time from 12 to three days. A single patient died, while another suffered gastrointestinal acute toxicity. They are now recruiting for a 52-person trial.
But not all radiation experts are convinced that findings from such a small study are worth running with just yet.
A number of experts, incuding Weischselbaum and colleagues from Duke, Stanford, and the University of Nevada, Las Vegas, wrote a letter about LDRT recently in the Journal of Radiotherapy and Oncology, describing the risks of the treatment as “unacceptable” for future clinical trials — especially in the absence of clinical or preclinical evidence that meets today’s experimental standards.
But with limited understanding of how LDRT interacts with the systemic inflammation seen in Covid-19, Weichselbaum said it’s possible that the therapy could put patients at risk of greater harm.
In their paper, Weichselbaum and his colleagues also expressed concern that radiation could kill the immune cells that the body deploys to fight Covid-19, rendering it more susceptible to attack.
There is research to suggest LDRT can combat the hallmark inflammation in people with arthritis.
Experts said there are also still a number of unanswered questions about the cytokine storm itself. Among them: Why do only some patients experience it, and what role might age, gender, genetics, and weight play?
another big ethical concern: Patients enrolled in radiation trials are being denied drugs “that might actually work in the long run.”
Kozono argued, however, that LDRT could prove faster-acting than the treatments currently being used, including the antiviral drug remdesivir.
the study will use such a low dose of radiation that the risk of cancer remains low, particularly when compared to the risks of a severe case of Covid-19.
“When one thinks about this being relatively low risk — one in 10,000 chance [of cancer] per year — compared to the very immediate life threatening consequences that this infection can pose, it may be a reasonable treatment to offer to the sort of patients we are aiming to help — people who are hospitalized, who need to be on oxygen or on ventilators because of pneumonia from this virus,” he said.
With so much still not known, McBride and other experts warn it is premature to champion LDRT over drugs currently in trial.