As the United States passes another grim milestone with more than 100,000 deaths due to COVID-19, one scientist thinks his idea could have saved lives. And may yet save lives in pandemics to come.
In a small village in France, Dr. David Fedson has been working for the past 16 years to promote a cost-effective strategy of using generic drugs to combat a pandemic.
“If we ran trials on promising drugs before the pandemic and found this approach to treatment didn’t work, well, so what? I was wrong,” Fedson says. “But if, after the pandemic, the research confirms that this approach actually does work, and then we look back at all those people who died unnecessarily, we’re going to feel very bad indeed.”
Drugs such as statins (a cholesterol lowering medication) as well as ARBs and ACEIs (blood pressure medications) are the drug types that he advocates running clinical trials on, as stated in his 2020 medical paper, “Hiding in Plain Sight: An Approach to Treating Patients with Severe COVID-19 Infection,” and other published work. While not averse to vaccines, he sees the mounting death toll as a case in point that to fight a pandemic there needs to be a medical option on “day one,” when the virus first starts spreading.
“The only way to effectively confront a pandemic is to figure out a way to use what we already have,” Fedson says. “Drugs that are generic, inexpensive, and that doctors use every day in their practices.”
Fedson is a retired professor of medicine from the University of Virginia who also served as the medical director at Aventis Pasteur, a European vaccine company. He saw the weakness of a vaccine-only approach to an influenza pandemic back in 2001 when he was instrumental in establishing the Influenza Vaccine Supply International Task Force.
“The whole purpose of the task force was to get the companies we worked for — and the top-tier executives running them — to pay attention to the fact that someday we would have an influenza pandemic,” Fedson says. “And it became quite apparent to me that the global capacity to manufacture pandemic vaccines just wasn’t there. By the time the vaccines would become available, it would be too late.”
Dr. Alice Huang, a virologist and former Harvard Medical School professor who was involved in developing a vaccine for HIV, confirms that an approved vaccine for the coronavirus will take time.
“We all really need something sooner rather than later, but in my experience with making a vaccine…it takes a long, long time,” Huang says. “And when you read about people saying that it would take about a year to 18 months, that is if everything goes perfectly right.”
Fedson recounted an early career experience treating cholera patients in India, not by targeting the pathogen, but focusing on keeping the patients alive long enough so they could overcome the worst effects of the disease.
“I spent three months on the Johns Hopkins Cholera Unit in Calcutta as the team fine-tuned a formula to rehydrate cholera patients, a breakthrough that has saved tens of thousands of people ever since,” Fedson says.
What made it effective is that the rehydration treatment could be lifesaving not just for cholera patients, but also for those suffering from severe diarrhea caused by other diseases. Regardless of what brought on the severe diarrhea — it could be a virus, shigellosis, or any number of other infections — the same treatment would keep the patients alive long enough until their own defenses took over and the diarrhea stopped.
The same concept of focusing on the well-being of the host instead of defeating the pathogen may be applied to treating COVID-19 as well.
In the case of COVID-19, when the immune system becomes compromised, its response can be too strong, causing a self-destructive form of inflammation that has been dubbed the “cytokine storm.”
Cytokines are small chemical messengers that tell the immune cells of the body to become activated, so they are ready to fight the virus. As is increasingly evident in some COVID patients, when that inflammation occurs in the alveoli of the lungs — the air sacs critical for delivering oxygen throughout the body — it can cause acute respiratory distress (ARD) and death.
Dr. Brian Ward, a professor at the Centre for the Study of Host Resistance at McGill University, who specializes in immune system response, says that a virus usually does not kill its host, but that COVID-19 is behaving atypically.
“It’s a weird virus; it’s not like many of the other viruses that we deal with,” Ward says. “Even though we’re closing in on one and three-quarter million people infected in the U.S. and five and one-quarter million worldwide, we do not yet have a clear idea of why some people seem to walk through the illness and other people get into real trouble really fast. And certainly, the idea of the body’s reaction, the so-called cytokine storm theory, is one of the hypotheses for that late inflammatory reaction in the lungs.”
Worldwide, there are currently more than 337,000 confirmed fatalities due to COVID-19 according to the World Health Organization’s May 24, 2020 coronavirus situation report, with the numbers likely to rise.
Instead of making the virus the primary target, which is what vaccines and antivirals do, Fedson says the top priority is to find a cost-effective generic drug — or a cocktail of drugs — that will reduce some of the worst consequences of the immune system’s overly zealous response to the virus and save lives.
“We’re talking about a way of treating people with acute critical illness due to any cause, and it can be a pneumonia, ARDs, it can be bacterial sepsis, it can be viral diseases, it can be lots of things that cause people to be hospitalized and get into ICUs,” he says. “The wonder and the beauty of it is that we’re using generic drugs that are available to people in Bangladesh, just as they are available to people in Boston.”
In the midst of the pandemic, Fedson’s idea may finally be gaining traction. Investigators at numerous U.S. universities — as well as in several countries outside the U.S. — have undertaken trials of angiotensin II receptor blockers (ARBs), a kind of cardiac medication that Fedson says might be especially effective when “repurposed” for use in pandemic illness. ACEIs and statins are being studied as well.
Two of the most important and innovative of these trials on ARBs are now underway with COVID-19 patients at the University of Minnesota trialing the blood pressure medication Losartan. As an ARB, Losartan blocks activity on a receptor site that raises blood pressure. It is possible that blocking this receptor will also diminish inflammation and reduce damage to the lungs of COVID patients.
“Losartan has an established safety profile and is readily available,” says Dr. Chris Tignanelli, an assistant professor at the University of Minnesota Medical School overseeing the trials and administering the drug to both in-patients and out-patients. “We wanted to test a readily available, cheap, FDA-approved generic drug with potential efficacy against COVID-19.”
Tignanelli was initially swayed by promising reports written by doctors in China who observed “a one-third reduction in lung injury” in SARS-infected lab mice who were given Losartan. The current trials are financed in part by the COVID-19 Therapeutics Accelerator Funds — a Bill and Melinda Gates Foundation initiative.
Dr. Michael Puskarich, the other doctor running the University of Minnesota’s randomized control trials, also sees potential for Losartan.
“Losartan is different from the other treatments being tested right now — it’s not an antiviral medication,” Puskarich says. “We’re trying to prevent the lung injury caused by the virus that makes it so deadly. We’re trying to turn COVID-19 into an everyday coronavirus, the common cold.”
The cost for a typical regimen of Losartan (14 tablets) is $15. Tignanelli says Losartan most likely will not be a “miracle drug,” but could be used as part of a cocktail of drugs.
“The story probably won’t end with Losartan,” he adds. “I doubt that any single drug is going to be a magic bullet as we’re probably going to need some combination of anti-inflammatory drugs targeting different parts of the immune pathway.”
Drug cocktails are something that hospitals such as St. Luke’s University Health Network in Pennsylvania are administering to their COVID-19 patients. At St. Luke’s, doctors have used a combination of vitamin C, zinc, atorvastatin, and steroids, as well as high-flow nasal oxygen and other pioneering approaches.
“Of course, the concept of using cheap drugs makes perfect sense, even to a random person on the street,” Fedson says, recounting a woman he met on a bus pre-pandemic who agreed it was worth a shot. “Unfortunately, she is not the president of the United States, and she’s not the director of the NIH [National Institutes of Health], or the director of the CDC [Centers for Disease Control], or the director-general of the WHO [World Health Organization]. I wish she were. If she had been, we would be much better off today than we are.”
Featured image: Shutterstock
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