Could Low Doses Of Radiation Raise COVID-19 Survival Rates?

Most discussions about the COVID-19 global pandemic, caused by the new coronavirus SARS-CoV-2, involve how to prevent spreading of the disease, as they should be.

The greater than 3% average case fatality rate of COVID-19 patients is quite large – by comparison, seasonal flu generally kills far fewer than 1% of those infected. But it’s COVID-19’s increasing fatality rates with age that are so worrisome – increasing to 8% for patients aged 70 to 79 and 14.8% for those aged 80 and over.

So researchers are increasingly trying to develop methods to reduce these fatality rates. While 80% of infected people have no, or only mild, symptoms, the rest can have infections that lead to severe inflammatory effects, pneumonia and death.

In those small number of patients, COVID-19 causes something called a cytokine storm. Such a storm is a deadly uncontrolled systemic inflammatory response of the body resulting from the release of great amounts of pro-inflammatory cytokines, which act as a major factor in producing acute respiratory distress syndrome, which is what kills.

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It’s why we need ventilators so badly.

Researchers are trying to target the pneumonia and stop or lessen the cytokine storm that leads to such high mortality rates. The problem is acute that we seem willing to try anything to get a handle on this pandemic.

We are even willing to try the anti-malaria drug, hydroxychloroquin, although it is unclear whether it works on COVID-19, or even how it works on malaria.

More promising treatments involve taking blood plasma from recovered COVID-19 patients to collect antibodies to develop future treatments, track the virus or possible re-inject into sick patients.

But we also need to revisit past treatments that have worked on pneumonia. Radiation therapy for pneumonia, particularly viral pneumonia like COVID-19 causes, was used during the first half of the 20th century with good results.

Dr. E. J. Calabrese at the University of Massachusetts School of Public Health & Health Sciences in 2013 discussed how X-ray therapy was used during this time to successfully treat pneumonia during the first half of the 20th century. Fifteen studies of about 700 cases of lobar and bronchopneumonia, sulfanilamide non-responsive, interstitial, and atypical pneumonia were effectively treated by low doses of X-rays.

Oppenheimer first started to use X-ray treatments in 1943 for pneumonia patients, and Powell even earlier in 1939. It was the anti-inflammatory effects that were so important.

Since then, low-dose radiation has been used for many medical applications, anything from cancer treatments to rheumatoid arthritis and other chronic autoimmune inflammatory diseases.

So the anti-inflammatory effects of radiation would be invaluable to helping patients COVID-19.

As stated by Calabrese, Dhawan, Kapoor and Kozumbo, “A possible mechanism by which low doses of radiation mitigates inflammation and facilitates healing is via the polarization of macrophages to an anti-inflammatory or M2 phenotype.” (see figure below).  Past studies also show that low-dose radiation regulates lymphocyte counts, controls bacterial co-infections, and can modulate excessive inflammatory responses, exactly what is needed for COVID-19 patients.

During the ongoing outbreak, Dr. Mohan Doss and Dr. Javad Mortazavi of Temple University Fox Chase Cancer Center in Philadelphia, have also looked at historic studies of low doses of radiation in the hopes of improving the immune response and reduce inflammation in COVID-19 patients.

These studies reported treating pneumonia patients by giving at least a 30 cGy radiation dose to the lungs using X-rays. The average cure rate for all the studies was 83%. In one study, X-ray treatments of pneumonia patients dropped the fatality rate from 28% to 6%.

Most importantly for COVID-19, the radiation treatment was for viral pneumonia patients who had not responded to sulfonamides. COVID-19 results in viral pneumonia.

While antiviral drugs, anti-inflammatory drugs and statins are systemic drugs that affect the whole body, radiation treatments are able to specifically target the lungs where the inflammation occurs. None of the radiation doses used are at levels that cause significant health risks by themselves, and all are at, or below, earth background radiation levels.

Mortazavi focused on low-level radiation treatments especially as a way to not mutate the virus into more drug-resistant forms.

This may strike you as counter-intuitive, but contrary to popular opinion and old wives’ tales, radiation is one of the weakest mutagens there is.

Their proposed method involves giving COVID-19 patients a single dose of 100, 180 or 250 mGy X-ray radiation. These levels are less than the maximum annual background radiation dose of many places on Earth.

In contrast to antiviral drugs, a single dose of X-rays cannot exert a significant selective pressure on the SARS-CoV-2 virus and hence does not lead to directed accelerated evolution of these viruses that could make them more dangerous and more resistant. You might be forgiven for not recognizing this area of biochemistry, even though it won the 2018 Nobel Prize in Chemistry. But a similar process of protein engineering is the reason microbes can become resistant to our drugs.

As we try lots of possible paths to rein in the coronavirus SARS-CoV-2, we need to use every tool we have, and low-dose radiation therapy appears to be worth exploring further.

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