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Editor's Note: After this video was posted, the NIH responded on behalf of Monica Bertagnolli, MD, who indicated she misspoke in comments made on viral persistence and long COVID, clarifying that she "meant to say viral components, rather than live virus. ... SARS-CoV-2 viral components (such as RNA and viral antigens) can be found in a subset of patients many weeks to months after acute COVID. These viral components may indicate the potential presence of persistent virus (or 'viral reservoirs'). The viral components may be a stimulus for ongoing immune dysfunction and are hypothesized to be a potential cause for some of the symptoms seen in long COVID patients. However, the presence of these viral components has not yet been shown to definitively correlate with long COVID symptoms. These are important areas of active investigation."

In part two of this exclusive video interview, 麻豆传媒 editor-in-chief Jeremy Faust, MD, talks with Monica Bertagnolli, MD, the 17th director of the National Institutes of Health (NIH), about the day-to-day work at the NIH on pandemic preparedness, the importance of looking for new approaches to testing, and the status of long COVID research.

Watch part one of the interview here.

The following is a transcript of their remarks:

Faust: Hello, this is Jeremy Faust, editor-in-chief of 麻豆传媒. We're joined today by Dr. Monica Bertagnolli. All right, I'd like to talk a little bit about the NIH and pandemic preparedness. Broadly speaking, is this something that the NIH is thinking about? Obviously there was some involvement, obviously during the pandemic, of the COVID-19 pandemic, including the NIH was hosting guidelines for COVID clinical policies and that sort of thing. What's the day-to-day work at the NIH on pandemic preparedness like?

Bertagnolli: So pandemic preparedness is an activity that takes place across all of health and human services and even involves other aspects of the government. I think one of the things that people might not realize is that the NIH director sits as part of an overall leadership team across health and human services. So for example, we work very closely with CDC and other team members across all of HHS on pandemic preparedness, and that's an activity that takes place all the time now during COVID, but also with any kind of threat that comes up, particularly from infectious agents.

Faust: What do you think we learned from this past pandemic that we could apply to the future?

Bertagnolli: Oh, many things. We learned about very rapid generation and deployment of testing materials through programs that were an amazing collaboration between NIH researchers and others across HHS. We learned about community level responses in 2020 through 2024, which are very different. Our world, our healthcare delivery system, our country is different than it ever has been before. So we learned about how to deliver care as well as vaccines across a really broad and diverse nation.

We also learned about some of the challenges of performing this kind of research, staying on top of variants that come and go, developing both vaccines as well as treatment modalities for the specific agent. And then finally, we learned a lot about conducting research. We learned we could do much more remotely, both to care for people and also to conduct really critical research.

Faust: Do you think that we did as well as some of our peer nations in terms of the research? Look, the U.K., I think, outclassed us in terms of just marshaling what they had to do platform adaptive trials of multiple things to figure out what didn't work, what did work. We did some of that in the government, but if there were a new pandemic tomorrow, would we be ahead in terms of -- all right, we're going to randomize 100,000 people to 50 different compounds and adapt these trials to figure out what works so that we can save lives sooner rather than later.

Bertagnolli: I think we did a lot during the COVID-19 pandemic. We continue to study COVID-19 as well as other emerging threats, and I think we'd do very well if we hit a challenge again. NIAID [National Institute of Allergy and Infectious Diseases] has a program that is going continuously to innovate in methods for vaccine generation, for identification and diagnosis of emerging threats, for observation from the community and clinical environment, and for being able to both monitor and respond very quickly. I think it's actually pretty exciting to see things that are going on behind the scenes here at NIH for all the new threats. And so I think we are going to be as ready as any government or organization could possibly be.

Faust: And does that mean that you are developing new approaches to testing? Because you did mention testing before as an area where we could, maybe -- we've done better over time -- but we could still do better next time.

Bertagnolli: Oh, absolutely. In fact, there's an entire network, the point-of-care testing network, that is run out of NIBIB [National Institutes of Biomedical Imaging and Bioengineering] that is constantly looking for ways, not only for infectious threats but for other health issues. Because diagnosis -- understanding the actual condition that is affecting people -- is almost as critical as treatment, and is certainly absolutely an essential prelude to any kind of successful treatment. So very, very active area of investigation across NIH.

Faust: In addition to the importance of researching SARS‑CoV‑2, other viruses, a lot of discussion about gain-of-function research. I know you've been on the record on this before. Can we actually learn anything about viruses without doing experiments such as gain-of-function and loss-of-function as well? Because it's a spectrum and depending on how you look at a virus, loss and gain are different things.

Bertagnolli: Oh, of course. We can learn a tremendous amount about viruses from any number of different methods of studying them. I do know that gain-of-function, looking at the hypermutable region of the genome of a virus that might code a particular area of importance for susceptibility, might be a good bet to kind of try to be able to get ahead of something before it truly emerges. But that kind of research certainly comes with risks and we have really worked hard to come up with very, very stringent oversight and containment procedures to make that type of research -- if it is to occur -- as absolutely safe as possible. You know, the bottom line is the benefit of any research like that has got to exceed the risk. And so that's why any kind of gain-of-function research for infectious agents is taken very, very seriously.

Faust: And in terms of long COVID, everyone always asks about this, there's a lot of funding. Where do you see this headed in the next few years?

Bertagnolli: It's a terrible, terrible condition. Post-infectious, chronic post-infectious syndromes have been around as long as there've been viruses in humans and it is a really, really terrible affliction when someone develops one of these conditions. COVID has introduced a whole new level of this in our society. The fundamental biology that's been conducted by the long COVID research team is really fascinating but also sobering. The agent can live for a long time in tissues. It can surround nerve cells, probably likely one of the ways that it produces some of its terrible symptoms such as the dysautonomia. And we have no effective way of eradicating it. Not yet.

One thing that's important though that's come out of several meta-analyses is there is a way to prevent it. And the way to prevent it is vaccination, and multiple vaccination is better than single to prevent long COVID.

Faust: I just want to follow up on something you said a moment ago about where this virus can be found in tissues. Are you suggesting that long COVID is actually, the mechanism of that, is persistent live virus in humans?

Bertagnolli: We see evidence of persistent live virus in humans in various tissue reservoirs, including surrounding nerves, the brain, the GI [gastrointestinal] tract, to the lung. (Please see Editor's Note above.)

Faust: OK. And you're saying this goes beyond the PCR's [polymerase chain reaction test] ability to get it in a regular swab so that we are missing chronic cases of SARS‑CoV‑2?

Bertagnolli: Correct. The virus can persist in tissues for months, perhaps even years.

Faust: OK. I think that's certainly one theory, but I'm not sure that that's settled. Is that fair? I mean, there's one thing between people who are autopsy, they died of viral sepsis, as opposed to people walking around. Is there a distinction there?

Bertagnolli: Our emerging data shows that the virus can persist into tissues in the long term, and I think that's really critical because it does help us think about possible ways to combat it, one being better antivirals. I think there's a lot of focus on developing new antivirals as a possible way of preventing long COVID, and the other might be more aggressive treatment with antiviral therapy upon initial diagnosis.

Faust: If that's the case, then it could be reactivated just like herpes is and shingles. Are we going to start seeing people get COVID not from infection, but from themselves in reactivation?

Bertagnolli: I don't believe I've seen or heard of any instance of that, and I don't think you can ever assume that one virus is going to act like another. Certainly every virus that we know of seems to have a different effect in the body long term.

Faust: All right, we're watching this story carefully. Let's end with a little bit more about your role at the NIH, your predecessor, Dr. Francis Collins. What advice did he have for you and do you stay in touch with him?

Bertagnolli: I do. I do. It's wonderful to be able to meet with Francis. Instead of giving me ideas, what he has been is just an incredible sounding board for thoughts that I have. And really, really encouraging of our various activities to promote data -- data use, more open data sharing -- to launch broader clinical trials networks, and not to let up on our supportive fundamental science because that really is the grounding of everything that we do.

Faust: Lastly, you left the National Cancer Institute [NCI] to take this job. What advice do you have for your successor there?

Bertagnolli: Oh, my successor is leading an absolutely spectacular team at NCI who are very, very passionate and incredibly knowledgeable, and also have an extramural community out there that has incredible talent. And so I just basically said, here's the keys. You're going to have such a wonderful time leading this amazing agency. And I know she has.

Faust: All right, well, Dr. Bertagnolli, thank you so much for joining us here on 麻豆传媒.

Bertagnolli: Thank you. Appreciate it. Take care.

Faust: OK, thanks.

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