Faust Files: Are We Now Better Prepared for the Next Pandemic?

In this video, MedPage Today Editor-in-Chief Jeremy Faust, MD, of Brigham and Women’s Hospital in Boston, sits down with two experts in the field of infectious diseases, Luciana Borio, MD, and Rick Bright, PhD, to talk about COVID-19 testing, the FDA, and lessons learned from the COVID-19 pandemic.

The following is a transcript of their remarks:

Faust: Hi, this is Jeremy Faust for MedPage Today, and this is part 2 of an interview with Dr. Rick Bright and Dr. Luciana Borio. They are pandemic and infectious disease experts. We are in the middle of a conversation here about what we’ve done right, what we can do better, and discussing their Viewpoints in the Journal of the American Medical Association — really focusing on how we can take word into action. So, let’s get right back into it.

Since you’re an infectious disease specialist, there is an issue of resistance, certainly that does not happen with vaccines, the way vaccines work and the repertoire of immunity that we get out of that. But is there a risk that our antivirals could not only become less useful, which we’ve already seen in terms of the monoclonals and other therapeutics becoming sort of already obsolete, but is there actually a possibility that our antivirals or therapeutics could breed resistance to this or other pathogens that we attempt with these strategies?

Borio: I’d say that it’s more than a possibility. I think it’s a probability. The idea of monotherapy for an RNA virus I think is concerning. And I would like to be able to see us move it into combination antiviral therapy to treat SARS-CoV-2.

I think it’s a matter of time before we begin to see resistance emerge, and to get to this idea of combination therapy — you know, this is what I call the work of government. It doesn’t happen without government intervention to bring companies together, to bring assets together, to help establish protocols for setting combination therapy, to help generate agreements between the pharmaceutical sector so they can collaborate on this, the regulatory pathways to get combination therapy approved.

That is the work of the government, and it needs to be done because it’s a matter of time before we lose valuable drugs.

Bright: I’ll jump in there too, just to add. Dr. Borio is exactly right. We should anticipate that the viruses will outsmart and evolve around these antiviral drugs. We will see antiviral resistance. It is an RNA virus, as Dr. Borio said, and especially as we start treating people with infections with antiviral drugs, we know we’re going to see differences in compliance.

There are people who will feel better, not take a full course of medicine. So there will be every opportunity for that virus to change and evolve and either be selected for new variants that evade the antiviral, or the antiviral could induce mutations in the virus, and we could see new variants emerge because of that treatment — especially incomplete or partial treatment with antiviral drugs.

I would imagine that the companies developing antiviral drugs already have done studies to show mutations that occur in the virus that has been exposed to these antiviral drugs.

I think the prudent thing to do, as we saw with the introduction of new influenza antiviral drugs, is to note those mutations that are likely to occur and to track and monitor those in the population. So we know when the rate of those mutations occurring or that potential resistance is occurring in the population, and we can track it and monitor to know when those drugs are losing their effectiveness.

And the best way to counter that whole process, as Dr. Borio described, is to have a cocktail treatment or a multi-drug treatment instead of a single treatment of antivirals.

We have two different antiviral drugs. They should be studied together, and we also need additional antiviral drugs urgently. We should have a rapidly accelerated plan, an Operation Warp Speed or a Manhattan Project or whatever name du jour we’d like to put on it, but we should come together.

We should make the development of a new, additional antiviral drug a high priority so we can have this cocktail approach, and we should put that on the list so we can really corner this virus instead of potentially pushing it to change even faster than what it might do without this.

Faust: One thing I think we also need to think about is the future. And so I do want to talk a little bit about testing since you covered that in your [JAMA] Viewpoints. And one thing that came up was wastewater testing.

I think it’s a really brilliant thing that we’ve been able to unroll. And the problem of course is lags and standardization. How do we operationalize this in a way that gives information in time? How does that work when it’s not standardized? And also when the thing you’re looking for may be something like Omicron, which actually might go undetected because it has some kind of deletion — how is that all going to work?

Bright: Jeremy, as you say, there are problems, there are challenges. It’s in some ways an old technology, but it hasn’t been used for this high throughput type of analysis.

Not every place has this infrastructure. How do we use wastewater in places with and without different sewage treatment plants? How does that impact the type of sampling and the concentration of those samples that we might find in the community? And then how do we synthesize wastewater data? We’re not getting like a full length viral genome sequence, like you would from a clinical specimen, like a nose swab or a throat swab; we’re getting fragments.

So it’s really important to come up with ways now to systematize how we analyze those fragments. How do we look for those knowns that you like we might know about today, like Omicron, and how do we pick out Omicron quickly, but how do we also sort through all of that noise for those signals, for something that might be emerging that we’re not watching for, and be able to know if that signal is something that we need to translate into an alert and what we do about it, and how do we validate and verify wastewater signals with traditional epidemiological clinical specimens, nose swabs or blood draws or whatever it might be?

Those are some of the things we still have to work out, but we’re just, at this point, happy to see that it works. It opens an option, an alternative. And we’re actually finding, surprisingly to me as an influenza expert, we’re finding influenza in the wastewater sampling now as well.

So it might open new ways to identify influenza outbreaks in a community. The goal here is to not necessarily identify a person, but to identify a community where something might be surging so you can get resources to that community and prepare them for the oncoming onslaught that might be seen.

Faust: As far as I understand — and correct me if I’m wrong — the FDA pathway for looking into testing that’s out there really is about diagnostics as opposed to monitoring for surveillance in the community.

For example, the pathways for rapid antigen tests, many have argued, are kind of inadequate or incorrect because it’s about diagnosing — that’s what the FDA does, but maybe there should be a different pathway for monitoring and for reporting just what’s out there.

So, Dr. Borio, what do you think about the FDA’s role in making tests more available in new pathways so that we have the tools that we need to detect threats both known and unknown?

Borio: Yeah, Jeremy. So, you know, I have to say that I really respect and admire the work the FDA does. It’s really easy to kind of beat the FDA. They don’t get it right all the time — of course not — but this idea that the FDA is the obstacle standing between us and these great diagnostic tests, it’s just not true. It’s a false narrative.

I think that they are also very understaffed and that is causing a problem right now for the more innovative tests, because we know that in private equity there is a desire to fund innovation, but they would like to have some regulatory path certainty, right? And a lot of these companies are not able to go and see the FDA right now because they’re so understaffed.

The FDA is prioritizing the established diagnostic developers. So that’s something that we have to add to the list for things to solve in the near future. Because I think we are leaving a lot of technology at the table right now that could make a big difference in the coming months to years.

Faust: Given what we’ve just gone through, we’ve become so politicized, but on the other hand, we’ve learned a ton. Do you think that a pandemic that broke out, say influenza, would go worse in 2025 or would it be worse to have had it in 2015? In other words, we’ve learned so much, but on the other hand, people aren’t in the mood to do anything. If there’s a new pandemic, what do you think would be worse: the technology and the know-how we’ve gotten today in a new pandemic, or if we had to do it all over, say in 2015? I’ll start with Dr. Borio.

Borio: I think we are in a really incredible place where a lot of science and technology was created and utilized these last couple of years. So I think it’ll be in a better place, and I’m an optimist. So even, you know, when you contemplate the flu pandemic of 20-something, I think we’ll do better. I have to think that we’re going to do better.

Bright: I’ll add to that. So I’m an optimist, but Lu and I have both lived through this and all of our colleagues have lived through this in the past. So we’ve seen other crises come, we’ve seen money flow in — and flood in, actually. We’ve seen a lot of technologies evolve. We’ve seen a lot of companies come together and put aside other profitable endeavors so they can respond to the moment.

We’ve seen government really make a lot of money and things happen. And then we’ve seen the crises go away or come under control or wane and have seen the interest dry up. We’ve seen the money dry up. We’ve seen companies go back to their regular business. We’ve seen government go back to business as usual.

And so we have an opportunity knowing all of that from the past, knowing what’s happened, what we learned in the last 2 years, to be in the place that Lu believes we can be in if we do not take our foot off the gas pedal in continuing to implement best practices.

Continue to take some of the things that we’re doing today with home tests and other prevention control measures and implement those into our daily life: upgrading our air filtration and ventilation systems in schools, public buildings, and public transportation, continuing the educational process about wearing a mask when you’re sick, and staying home when you’re sick and getting tested so you can get treated sooner, etc. We need to implement those.

If we do so, and the financial support is sustained to do so, and the capacity and capabilities we built around the world to make these drugs and vaccines and diagnostics even better and faster — if we sustain those so they’re here and ready and warm when that next pandemic comes through in whatever year it might be, then we will detect it earlier. We’ll have the tools to respond, and people will know what to do, and we will be in a much better place.

Faust: And that really leads me to my last question, which is: you’ve both authored amazing articles, you’ve achieved a lot, these recent JAMA Viewpoints have been highly influential — but how do we translate words into action so that these aren’t just words on a page? What is the way to take these in some ways brilliant and provocative ideas, some of them very achievable and some more aspirational? But Dr. Borio, how do you see these words on a page becoming action? What’s the path?

Borio: They have to, right? Words on a page, PowerPoints, don’t save the world. But Rick and I had been in the U.S. government working in crisis in the past and we know what happens — amazing things happen, when everyone comes together, when they apply resources.

It’s really remarkable to see what can be accomplished when the U.S. government makes a decision and leads the way. I think that we need to continue to press for this to happen, because we are still in the middle of a crisis, and we don’t know when the next one is going to be at our doorstep. So we have to keep building the programs to defend us against these types of threats.

Faust: Well, thank you both for joining us here with MedPage Today. I think your expertise is unmatched, unparalleled, and your leadership and even your optimism after everything we’ve been through is very reassuring to me. I anticipate that the places where we listened to you are the places we will have improved.

So thank you both for joining us and also for all the work you’ve done on behalf of everybody.

Watch Part 1: Would a ‘New Normal’ Mean Doubly Deadly Flu Seasons?