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Re: Medicines/Supplement that might help 4 coronavirus

Posted by Hugh on September 17, 2021, at 11:54:13

In reply to Re: Medicines/Supplement that might help 4 coronavirus, posted by Hugh on March 9, 2021, at 10:41:36

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.

Antibiotics can help treat cases of pneumonia from bacterial infections, but not those caused by viruses. Those experts argue compelling historical data gives LDRT a promising head start.

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.

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 severe illness and death that we see from Covid-19 pneumonia appear to be mostly due to the inflammatory response to the infection in the lung tissues," said radiation oncologist David Kozono, who is launching a LDRT trial at Brigham and Women's Hospital. "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.

"The history of the utilization of ultra-low-dose radiation for viral pneumonia actually dates back to the 1920s and '30s and '40s -- just post the Spanish flu pandemic in 1918," Chakravarti noted. He said literature from that era indicates that LDRT was effective in 75 to 90% of influenza-induced viral pneumonia cases, though the therapy "fell out of favor" after the development of antiviral therapies and vaccines.

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.

"So there is now accumulating data to support this type of approach not just in the setting of influenza viral pneumonia, but also in the setting of specifically Covid-19 based on the small but very promising study from Emory University," he said.

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.

A comment on the article from Fred Willison:

I've been a radiation oncologist for 30 years and have treated many patients with low dose radiation therapy for its well known and well established anti-inflammatory effects. The mechanism is generally thought to be due to the extreme radiosensitivity of white blood cells, in particular lymphocytes which are one of the very few cells that die an interphase death immediately after radiation exposure. The sensitivity of these cells relative to other somatic cells in the human body is such that extremely low doses of radiation can be quite effective for immune suppression with relatively little risk of injury to other cells.
Another piece of information that might be useful is the experience from whole lung radiation therapy for other medical problems. Whole lung radiation has been part of the standard treatment for certain curable pediatric malignancies, notably Wilms tumor, for decades.
Personally, I think it is highly likely that a meaningful and rapid (almost instantaneous) lung-targeted, anti-inflammatory response can be achieved with this technique and that the acute toxicity with proper dosimetry will be extremely low. I personally doubt that exacerbation of viral replication due to inflammation-suppression will be a major issue, which is not really different than the question of steroids/dexamethasone which appears to have already been answered.
The issue will be whether the targeted anti-inflammatory effects, which are quite predictable, will be the needed intervention at the particular time in the disease course it is applied.
The other issue is whether the long term risk of carcinogenesis from the low dose radiation exposure is justified (similar to the risk/benefit analysis we routinely make in malignant disease). The risk is very low and the interval between exposure and malignancy induction is typically many years, often decades. If a patient with severe covid 19 is on a ventilator and deteriorating despite other interventions, the small risk seems more than justified.
Testing in primates is great, but given the clinical scenarios at issue many people will die while we wait for that data. Ethics and purity of science in this situation is not cut and dried.

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