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COVID-19 vaccines will be critical to ending the pandemic. In the meantime, we can’t afford to slow our search for treatments

David Fajgenbaum, MD, MBA, MSc
January 27, 2021

A researcher is poring over every possible treatment for COVID-19. Some may be hiding in existing medications, he argues. Here’s why the quest for him is so personal — and what he believes must happen next.

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In 2014, David Fajgenbaum, MD, MBA, MSc, uncovered a potential treatment for his own deadly disease. Now he's on a mission to find one for COVID-19.
In 2014, David Fajgenbaum, MD, MBA, MSc, uncovered a potential treatment for his own deadly disease. Now he's on a mission to find one for COVID-19.
Courtesy: David Fajgenbaum, MD, MBA, MSc

Editor's note: The opinions expressed by the author do not necessarily reflect the opinions of the AAMC or its members. 

Widespread vaccinations certainly provide our greatest chance of defeating COVID-19. But even with current plans to distribute 150 million vaccines in the next 100 days, most of the country will likely remain unprotected through the spring. Given the current high rate of infections, the unfortunate reality is that as many as 100,000 more people are likely going to die in the next few months.

Our best hope of saving these lives is to find more effective treatments. And treatments will be even more critical if vaccination is not widely adopted — or mutations decrease the effectiveness of the vaccines.

This issue is particularly personal for me. First, I’ve nearly died five times from an illness that ignites an immune response in which the body attacks itself — a cytokine storm — just as COVID-19 often does. I have dedicated my scientific career to understanding and treating cytokine storms. Second, my illness — Castleman disease (CD) — increases my risk of dying should I develop COVID-19. What’s more, I have survived for as long as I have because I found a medication that could be repurposed for my disease.

Given the current high rate of infections, the unfortunate reality is that as many as 100,000 more people are likely going to die in the next few months. Our best hope of saving these lives is to find more effective treatments.

In 2012, when I relapsed on the only medication being studied for CD, I knew I needed to turn my hope for a treatment into action. I quickly began searching for an existing drug that could be repurposed for me and other patients. The drug I take every day now, sirolimus, was approved by the Food and Drug Administration (FDA) for another condition, but because research on CD treatments was slow and uncoordinated, it was hiding in plain sight.

Drug repurposing can work well because the biological targets of medications often are central in more than one disease. Repurposing drugs is also faster and cheaper than developing them from scratch. On average, it takes 10 to 15 years and more than $1 billion to develop a new FDA-approved drug. As with COVID-19, those hoping for a CD treatment didn’t have that kind of time or money.

Fortunately, there are more than 2,500 FDA-approved drugs. Unfortunately, though, there are few financial incentives for repurposing medications since many of them are generic. That means it takes a concerted, coordinated research effort to find an existing medication that might work. When I started my search, I desperately hoped one was out there for my disease — and I found myself hoping for the same thing when COVID-19 hit.

This issue is particularly personal for me. First, I’ve nearly died five times from an illness that ignites an immune response in which the body attacks itself — a cytokine storm — just as COVID-19 often does.

Wanting to do my part, I redirected my Center for Cytokine Storm Treatment and Laboratory at the University of Pennsylvania to focus on identifying new or repurposed treatments for COVID-19. In March 2020, we launched the CORONA (COvid19 Registry of Off-label and New Agents) project. Now it’s the world's largest database of COVID-19 treatments, covering more than 350 medications that have been administered to more than 300,000 patients.

CORONA has since been used over 20,000 times by scientists at Google Health, the FDA, and elsewhere to inform clinical trials and patient care. The CORONA team has included more than 90 individuals — volunteers, medical students, and staff — who often work on nights and weekends. We have been combing through huge amounts of data looking for the most promising treatments.

And we’ve found some compelling insights that can help combat this deadly disease.

So far, a handful of drugs have likely helped save tens of thousands of lives. Most clearly effective is dexamethasone, which works by calming patients’ overactive immune systems. Because CORONA pulls together many datasets into one central place, we were able to quickly identify dexamethasone as highly promising, before it was proven effective in a large clinical trial. But because this medication helps only a subset of the most severe COVID-19 patients, other treatments are urgently needed.

We’ve now identified 10 additional medications that, in collaboration with scientists at the FDA and elsewhere, we’re hoping to move into large, well-designed trials to test their effectiveness. These include drugs that boost the immune response, like interferon (approved for leukemia) and ones that suppress the immune response, like baricitinib (approved for rheumatoid arthritis). They even include psychiatric medications, like fluvoxamine (approved for obsessive compulsive disorder), that seem effective for reasons that are not yet clear.

In addition to identifying promising medications, we’ve also uncovered several other significant insights into treating COVID-19.

First, treating COVID-19 isn’t just about targeting the SARS-CoV-2 virus. A significant concern is that while some patients suffer from an immune reaction that’s too weak, others mount too strong a response, which may badly damage their organs. That means the best treatment for COVID-19 can vary greatly depending on a particular patient's immune response.

Second, timing matters — a lot. For example, immunosuppressants are likely harmful if given early but helpful if given later, and the opposite is true of immune-boosting medications.

Finally, the CORONA team has also revealed significant inefficiencies in COVID-19 research. For example, some drugs that have been found ineffective in multiple large clinical trials still are being explored in dozens of studies. Meanwhile, many drugs that have shown promise in small clinical trials haven’t yet had larger trials launched to study them.

We have been combing through huge amounts of data looking for the most promising treatments. And we’ve found some compelling insights that can help combat this deadly disease.

We are now expanding CORONA beyond its original scope — treatments administered to humans — to include data from lab studies as well. The goal is that this expanded tool will enable government agencies, researchers, philanthropic organizations, and biopharmaceutical companies to access all COVID-19 treatment data in one central place, thus enabling better prioritization of research, less duplication, and easier collaboration across institutions.  

Fortunately, President Joe Biden released an executive order on his second day in office calling for expanded research into treatments for COVID-19. For researchers to identify much-needed treatments, we will need to systematically track every treatment being studied in one central place, quickly identify promising options for trials, and provide the funding and infrastructure necessary to ensure that large, well-designed, randomized controlled trials are performed for these treatments. Like vaccinations, such efforts are essential to turning the tide against this pandemic.

This month marks seven years that I’ve been disease-free on my current CD treatment. Now I desperately hope that our work and the work of researchers around the world will enable many years of disease-free life for COVID-19 patients. We must keep doing everything we can to turn that hope into action.

David Fajgenbaum, MD, MBA, MSc, is an assistant professor of medicine at Perelman School of Medicine at the University of Pennsylvania and author of the national bestseller Chasing My Cure: A Doctor’s Race to Turn Hope Into Action, which is out in paperback this week. You can follow him on Twitter at @davidfajgenbaum.

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