Anthony Fauci discusses challenges of COVID-19, reasons for hope during Stanford Medicine event

The nation’s top infectious disease expert spoke with School of Medicine Dean Lloyd Minor about the challenges posed by COVID-19, the hope for emerging vaccines and treatments, and what’s still unknown about the virus.

- By Hanae Armitage

The COVID-19 pandemic is an infectious disease scientist’s “worst nightmare,” said Anthony Fauci, MD, the nation’s top infectious disease expert, during a conversation with School of Medicine Dean Lloyd Minor, MD, on July 13.

 “Of all the emerging infections that I’ve had to deal with in the 36 years that I’ve been the director of the institute — starting off from HIV in the early ’80s with Ebola and Zika, and anthrax attacks — this is clearly the most challenging,” said Fauci, director of the National Institute of Allergy and Infectious Diseases and member of the White House Coronavirus Task Force.

During the discussion, which was streamed live online, Minor called attention to the critical role that Fauci has played as a voice of authority about the pandemic, thanking him for his guidance and contributions during this crisis. “In fact, a recent poll showed that Americans cite Dr. Fauci as the most relied-upon official for information regarding the COVID-19 pandemic — and for very good reasons,” Minor said. 

Fauci pointed to a host of challenges that the nation faces in dealing with the virus, including the need to devise an effective and widespread vaccine, the need for more early-acting treatments to curb severe infection, and the lack of a public health infrastructure for handling an outbreak of such proportions. In addition, even as other countries see a decline in case numbers, many American states are seeing a surge, largely attributable to the fact that the United States never fully shut down, he said.

But there are also reasons for hope and opportunities for progress, he said.

Fauci and Minor discussed how randomized controlled clinical trials led scientists to find that two drugs, dexamethasone and remdesivir, provide benefits to patients with moderate to severe coronavirus infection, and more drugs are under investigation. 

“We have such extraordinary talent in our academic medical centers; we really need to begin to leverage them more,” said Fauci, when Minor asked about the role of centers such as Stanford can play in the pandemic. The more we do that, Fauci said, the better off our response to the pandemic will be.

Following is a transcript of the conversation. It has been lightly edited for clarity.

Lloyd Minor: Welcome to StanfordMed LIVE. I’m Dr. Lloyd Minor, dean of medicine at Stanford University. I’m delighted to be joined today virtually by Dr. Anthony Fauci. Before we jump into today’s discussion, I want to express my gratitude to Dr. Fauci for his leadership as a member of the White House Coronavirus Task Force. His expertise and role as a public spokesperson have been invaluable these past several months. In fact, a recent poll showed that Americans cite Dr. Fauci as the most relied upon official for information regarding the COVID-19 pandemic — and for very good reasons. Having served as the director of the National Institute of Allergy and Infectious Diseases, or NIAID, for more than 35 years, Dr. Fauci has led our nation’s response through a number of health crises. In the 1980s, for example, his work was instrumental in addressing the HIV/AIDS crisis, which hit our Bay Area community especially hard. Today we will discuss the state of the COVID-19 pandemic, our progress against this disease and what the future of health care will look like in its wake. Dr. Fauci, thank you for being with us today. We’ve received over 2,000 questions submitted in advance of today’s fireside chat, and we’ve tried to organize them into several themes. Now, let’s get started. Dr. Fauci, you’ve been called America’s doctor. You’ve advised six different presidents. We hear reports of 18-hour workdays, which must be filled with countless demands on your time. Do you have time to reflect on the unprecedented nature of what you’re managing? How are you dealing with the stress or confines of the pandemic given how much you’re in the spotlight?

2:03  

Anthony Fauci: Well, that’s an interesting question. Thank you for having me here with you. Yes, this is unprecedented. One thinks about the worst nightmare of an infectious disease person who’s interested in global health and outbreaks: It’s the combination of a new microbe that has a spectacular degree of capability of transmitting, and has a considerable degree of morbidity and mortality. And here it is, it’s happened — your worst nightmare, the perfect storm. It’s one of those things where you’re really just functioning on adrenaline. This is a really serious problem. It is truly historic. We haven’t even begun to see the end of it yet. It’s still globally threatening. Some countries are doing better than others, but until you get it completely under control, it’s still going to be a threat. So, it is truly unprecedented. We’re doing what we can, and I’m sure we’re going to get into this with the other questions, but as you mentioned in the introduction about HIV, of all the emerging infections that I’ve had to deal with in the 36 years that I’ve been the director of the institute — starting from HIV in the early ’80s, with Ebola and Zika, and anthrax attacks — this is clearly the most challenging. It’s the most challenging because it’s so pervasive. I mean, it is truly a global pandemic, and really when I say unprecedented, I mean dating back to the 1918 historic pandemic, which was called the Spanish flu. I think 50 years from now, people are going to be reflecting historically on this, the way we used to reflect on the 1918 outbreak.

3:53  

Minor: Perhaps we could start with a level set on where we are right now with this pandemic. We’re all concerned about the increasing numbers of COVID-19 cases. What are your thoughts about how we navigate this surge? And what are your predictions about the COVID-19 pandemic and how it’s going to evolve in our country and the world in the months ahead?

4:13  

Fauci: Good question. If you put aside for a moment the issue of how things could be completely turned around when we get a safe and effective vaccine, and talk about what’s happening today in the absence of a vaccine — what we can foresee in the immediate future is very clear. We know from countries throughout the world that you can physically separate people to the point of not allowing the virus to transmit, and the only way to do that is by Draconian means of essentially shutting down a country. We know that we can do that if we shut down. The Europeans have done it. People in Asia have done it. We did not shut down entirely, and that’s the reason why, when our cases went up, we started to come down and then we plateaued at a level that was really quite high, at about 20,000 infections a day. Then as we started to reopen, we’re seeing the surges as we speak, in California, your own state; in Arizona; in Texas; in Florida and in several other states. So that when you try to reopen, if you’re not handling the surgency well, what you’ll see is what we’re seeing right now. So we need to drop back a few yards and say, OK, we can’t stay shut down forever economically. There are secondary unintended consequences on health and on a variety of other things that make it completely untenable for us to stay completely shut down for a very prolonged period of time. So you’ve got to shut down but then gradually open. And we made a set of guidelines a few months ago, with good, what we call, checkpoints. We had situations where you do entry, and you would have phase one, phase two and phase three. Unfortunately, it did not work very well for us in an attempt to do that. But we can get a handle on that — I am really confident we can. If we step back, you don’t necessarily need to shut down again. But pull back a bit, and then proceed in a very prudent way, of observing the guidelines of going from step to step. All you need to do is look at what’s on TV — people in some states who went from shut-down to completely throwing caution to the wind, such as bars that were crowded, people without masks. There are things you can do now: physically distancing, wearing a mask, avoiding crowds, washing hands. Those things, as simple as they are, can turn it around. And I think we can do that. And that’s what we’ve got to do, looking forward.

7:15  

Minor: Understood. If we look six months from now, if we do the things you recommend — and that’ll transition us into discussing therapeutics and ultimately a vaccine — but what’s your outlook for six months to a year from now? And how hopeful are you about therapeutics that may come on board before we get an effective vaccine or vaccines?

7:39  

Fauci: Your points are very well taken. Right now, we’ve shown through randomized, placebo-controlled trials that there were two interventions that clearly have a significant benefit in people with advanced disease. When you’re dealing with dexamethasone with patients either on a respirator or requiring oxygen, and when you’re dealing with remdesivir, which best affects patients who are not on ventilator but may have low-flow oxygen requirement, what we really need, and we’re on the track of getting, are interventions that can be given early in the course of disease to prevent people who are vulnerable from progressing to the requirement for hospitalization. And those are direct antiviral drugs, convalescent plasma, hyperimmune globulin, monoclonal antibodies and a number of direct-acting antiviral agents. I believe we are on a good track to get there reasonably soon. I already mentioned the two drugs for advanced disease, but we really want to get stuff early. Vaccines, as you know — there are multiple candidates that are in various stages of clinical trial. One or two of them will go into phase three, for efficacy, literally at the end of this month. So we’re pretty cautiously optimistic that at the end of the year, beginning of this coming 2021, we will have one, and maybe more, vaccines that will be available.

9:12  

Minor: Dr. Fauci, you’re known for your candor. How’s the Bay Area doing in terms of our response? Can you give us a grade?

9:20  

Fauci: No. (Laughs.) I get into trouble when I grade people. It’s a little bit presumptuous to do. California, being the large state that it is, is a bit of a mixed bag. You know, relatively speaking, the Bay Area is doing better than other areas in the southern border with Mexico, where we’re seeing a lot of a situation where the surge is really rather significant there. So I think it really is a big difference because when you get a state like California or like Texas, it’s so large, you can’t unidimensionally make a statement about it. But I can tell you one thing is true — on a positive note: I’ve worked with Governor Gavin Newsom throughout these last few months, and he really has his handle on it and understands what he needs to do, and I believe is doing a really very good job, as are several of your mayors, actually.

10:22  

Minor: Thank you. As you know, in early March, Stanford was one of the first academic medical centers in the U.S. to develop its own diagnostic test, which helped make testing available in Northern California in those early and very trying months. What role can academic medical centers play in the current crisis? And how can we advance pandemic preparedness moving forward coming out of COVID-19?

10:46  

Fauci: Well, that’s a great question. And I’m glad that you asked that. We have such extraordinary talent in our academic medical centers. We really need to begin to leverage them more. Several such as in New York City — New York Presbyterian, Cornell and Columbia and places like that, NYU — they really got involved and were very contributory to getting our arms around the outbreak. California has a number of world-class academic medical centers. I mean in the Bay Area alone, you have UCSF and Stanford, right there, two among others that are some of the best in the world. And I think getting them involved, which they are actually, many of them. You mentioned the idea about the diagnostic test. I think if the rest of the country would leverage their academic medical centers to get involved, we’d be much better off.

11:46  

Minor: Dr. Fauci, you are a physician-scientist and an exemplar of the physician-scientist role model. What are your thoughts about the training of the next generation of physician-scientists? What can we be doing to encourage that training, make it more effective and make sure we’re prepared in the future when pandemics like this arise?

12:07  

Fauci: Well, that’s a great, great question. Training physician-scientists in multiple disciplines — I can’t hit every discipline — but the discipline of response to outbreaks, I think is so important that so many of our people now are just amazingly performing and just doing a great job. We’re learning on the fly, learning on the job, building the plane as they’re flying it. I think what we really do need, and I’ve been saying this, quite frankly, for a couple of decades, we really need to have a very solid pandemic-preparedness plan and operational capabilities, because this is not something that is going to go away and never happen again. We’ve had outbreaks before, none as serious as this, but we’ve really got to use this as a lesson to be prepared for the next one as we learn our way through this one.

13:08  

Minor: What types of things do we need to do to be better prepared? If we look at all the way along the spectrum from basic research, translational research clinical trials, the public health infrastructure in United States, it’s a vast topic. But can you share some ideas about the tangible next steps that we need to be planning for now, so we don’t run into this predicament a decade or anytime in the future?

13:31  

Fauci: You know, I could address it from multiple vantage points. But let me take the one that I’m most familiar with as a physician-scientist. That is, what can we do from a scientific standpoint? There are many things that you could do that would be applicable to a response to any outbreak, things that we started to do, and I think have fared us well, in the rapidity of our response in the arena of vaccine development. And that is to develop new avant garde upfront, really sophisticated platform technologies, where you can hit the ground running with vaccine development and not have to worry about growing out the pathogen and inactivating it or attenuating it. We have a number of platform technologies that the more you perfect them, the easier you can make the transition from an unknown agent into a vaccine that’s operational. That’s one thing. 

The other thing is to study what you call prototype pathogens. In other words, to get really good at understanding a particular family of potentially threatening microorganisms. I’ll give you an example: the coronaviruses. This is the third pandemic we’ve had in the last 18 years with coronaviruses. We had SARS in 2002. We had MERS in 2012. And now in 2019 and 2020, we got COVID. So it just makes sense that if you want to create something like a universal vaccine for something like a coronavirus, we’ve got to do that now. And when we get through this, the same thing has to be done for flaviviruses, such as Zika and West Nile and Japanese encephalitis. We’ve got to be able to do universal therapies and universal platform technologies for these. That’s the fundamental basic science. I won’t do it, but I could use up all the time just talking about building a better public health infrastructure, too. We have let the local public health infrastructure in our country really go into tatters. It’s one of those things where you’re a victim of your own success. We were so good at controlling smallpox, polio and tuberculosis that we let the infrastructure locally, essentially, go unattended. And it attenuated and attenuated, and now when we need good local public health capability, it’s not optimal. It’s not as good as it should be. We’ve got to build it up again.

16:35  

Minor: When you look at the data in the communities hardest hit by the coronavirus, it really highlights issues of health care inequality and access to care in our country. What can we be doing now and in the future to better address this situation?

16:51  

Fauci: Good question. And I like the fact that you said now and in the future. There are things we can do now by concentrating resources in those demographic areas which are suffering the most. It’s like a broken record; it’s the same thing. Minority populations are disproportionately negatively impacted by diseases like this. And in your state, it’s mostly African Americans and Latinx, with some Native Americans. And when I say it’s like a broken record, it’s because I’ve been through this now in two major ways. HIV — which is what I started off with in the early 1980s — now today in our country, 13% of our population is African American, and 45% or more of the new cases are among African Americans. Of them 65% are men who have sex with men. Of those, 75% are young. Take COVID-19 — same thing. If you look at the incidence of infection on the basis of how, in general — you don’t like to generalize, but here you have to generalize — how the African American population and the Latinx population find themselves with jobs that don’t allow them to properly protect themselves. As everybody’s locking down, they’re doing the essential jobs that require their physical presence. So they’re immediately at more risk of getting infected. When they do get infected, when you look at the prevalence and incidence of co-morbidities that make you at higher risk for a poor outcome, they have most of them, more than the Caucasian population: hypertension, diabetes, obesity, chronic lung disease, kidney disease. It’s striking how disproportionately they are disadvantaged.

19:00  

Minor: We recently held our annual rite of commencement for the 2020 School of Medicine graduating class. What advice do you have for the next generation of physicians, scientists, researchers — not just at Stanford, but across the country?

19:15  

Fauci: Well, you know, I mean, I’m obviously quite prejudiced on this because it’s what I’ve been doing. But the opportunities in medicine, if you just want to do medicine, and just see patients, that’s an incredibly noble profession. And you could tell right now with what we’re going through, how important those frontline health care workers are. If you’re interested in the scientific bent to what you want to do, never before in history have the scientific opportunities been so spectacular as they are right now. So much so that I often fantasize — I like to turn the clock back and be 25 years old again, starting all over again. I know many of the young people would say, this guy is crazy to want to do that. But the fact is, it’s so exciting that things even now with my experience and what I’ve done, I still am in awe at what’s coming out from a scientific standpoint.

20:18  

Minor: Dr. Fauci, you’ve mentioned already several times about the HIV/AIDS pandemic, your important role and the important role of your institute. One role that that you and the institute have played very importantly, in HIV/AIDS, and now with COVID-19, is in clinical trials. In fact, you were instrumental in redesigning the clinical trials infrastructure in our country during HIV/AIDS. How do you think about now, with COVID-19, the structure we have for clinical trials? You mentioned before — and perhaps we’ll cover in a little bit greater detail now — the focus on outpatient therapeutics, but is our structure of the way it should be? What do we need to tweak? What are we learning in real time from this pandemic about what needs to be changed moving forward about the clinical trials infrastructure, its funding, its oversight in our country?

21:10  

Fauci: I think what’s very clear, and I just am so pleased that we’re able to show it: Not too long ago, there was the incorrect assumption that you can’t do research in the middle of a pandemic, or an epidemic outbreak, because it’s very important to whatever treatment you have, whether it’s proven or not, get it to the people because they need it and it’s better than nothing. That’s an understandable approach. But it really is flawed. Because the best research you can do is in the middle of an outbreak because you want to help the people who are experiencing the outbreak, but you want to learn from it, so that you can help that many more. Until recently, it was felt that ethically, even, you shouldn’t do research in an outbreak. And we proved that wrong in the Ebola outbreak. We did randomized placebo controlled trials, we proved that a couple of therapies worked, a vaccine was developed, and now already with COVID-19, the two drugs that have now definitively shown to be beneficial in advanced disease were proven by a randomized placebo-controlled trial. So clinical research and clinical research infrastructure is a very important part of the response to outbreaks. And we’ve already proven that, and I think we need to make sure we appreciate that going forward.

22:45  

Minor: If we think about those clinical trials and focus for a moment here in the outpatient setting, you mentioned before briefly some of the things that are being developed, maybe we could discuss those in a bit greater detail. There are monoclonal antibody therapies being developed and in early stage trials now. There are also trials looking at repurposing of other antiviral agents to see if they’re effective in COVID-19. What are you most enthusiastic about? And what are your thoughts about the pace of these trials and whether or not maybe by the fall or winter, we will have a regimen that could be beneficial in the outpatient setting, to a person newly diagnosed with COVID-19? Fortunately, not sick enough to go into the hospital but hopefully increasing the probability that they won’t have to go into the hospital and that their recovery time will be shortened. Where are you most hopeful? Where do you see the progress being made?

23:37  

Fauci: Well, given the experiences that we’ve had with Ebola and monoclonal antibodies, I think that that’s almost a sure bet: monoclonal antibodies directly against the virus, to be given in a single or a couple of intravenous infusions to people early in the course of disease, to prevent the necessity of their going into the hospital in advance. So right away that’s up front — they’re going into multiple clinical trials now doing that. Convalescent plasma, I think we need to have some caution about that; you want to make sure you do it right, you’ve got to get the right titer of antibody, because there’s amazing variability in titer of antibodies in people. So the best way to get that done — it’s a little bit more work — is to get the convalescent plasma and do hyperimmune globulin that you could titrate and know exactly what you’re giving to people. The thing I’d like to see more of, and we will see it, is screening of molecules that are pure antivirals that can be given early on. You know remdesivir is an antiviral, but there are polymerase inhibitors and protease inhibitors, and things like that very similar to what we did with HIV that I’d like to see pursued a bit more. So I think by your timeline that you mentioned, sometime in the fall, I think we could conceivably have a couple of more good antivirals as well as anti-inflammatories.

25:07  

Minor: You discussed work toward a vaccine or vaccines earlier in our discussion today. Perhaps we could follow up on that by you giving us your thoughts on when a vaccine or vaccines are available. There will be a massive push for distribution for immunization. What type of an allocation methodology should be set up? And how are you thinking about bringing online and distributing throughout the United States and in the world the vaccines as they move through the various stages of trials and hopefully get to FDA approval?

25:44  

Fauci: Well, one of the encouraging aspects about the approach to these multi-candidate vaccines is that the companies that are involved, with substantial financial help from the federal government, are making a commitment to start producing large numbers of doses of the vaccine even before it’s definitively proven to be safe and effective. So the risk is a financial risk. Because if you make a lot of doses and it’s not safe and effective, you’ve lost a few hundred million dollars. If you make a lot of doses ahead of time and it proves to be effective, you’ve gained multiple months in the process. So assuming, now, I’d like to make a reasonable assumption that sometime at the beginning of 2021 we have a couple of vaccines that are safe and effective. The distribution will have to be done in an as equitable way as possible. Obviously, you ultimately want to vaccinate everybody, but as doses come online, you’re going to have to prioritize. And that’s where you put together committees of people who understand vaccinology; community representatives; and, above all, ethicists, who can make sure your decisions about distribution are based on ethical principles of justice and fairness, etc.

27:17  

Minor: Of course, having a vaccine that’s been shown through rigorously controlled trials as effective is a necessary first step. But we also know that in America today, there’s a lot of skepticism about vaccines. What can we as physician-scientists, as leaders, do to reassure and regain public trust in vaccines, which, as you’ve said, are almost certainly going to be essential to the control of this pandemic?

27:46  

Fauci: Well, it can be stated in a few words: community engagement. We did that with HIV when we had treatments and prevention. We’ve got to engage the community, to get out there and be people who have boots on the ground, who look like and are like the people that they’re trying to convince of the importance of getting vaccinated, particularly in this era of antivax and anti-science. We now have a network of community workers who are getting ready and prepping them up, to go into the community, and try and convince people why it’s important for them, and for their families, to get vaccinated. But you’ve got to do it in a way that fits the community. As I often say, you don’t really want a lot of white guys in suits like me, going into a mostly minority community, and convincing them about something that they’re very deeply skeptical of. You’ve got to get people that the community trusts.

28:51  

Minor: Dr. Fauci, if you could look at the scientific unknowns today about this virus and about its disease, COVID-19, what are the top four or five things that if we knew today, we would be much better off in the future, recognizing that the knowledge continues to evolve and the entire pace of this pandemic I think is unprecedented for all of us in terms of first showing us how little we understood about the virus and about its manifestations as COVID-19. We know more now, but there’s still a lot of questions to be answered. I was wondering what your thoughts are on what the critical questions are at this juncture.

29:32  

Fauci: Sure. The critical question, obviously, you just mentioned a little while ago: Will we get the body to induce a durable response that can protect you, whether that response is following recovery from natural infection and/or induction of immunity by a vaccine? Is it possible to have durable, effective immunity? I think it is, but it’s still an unanswered question that we need to prove. Number two, what about the chronic long-term effects of people recovered? We’re only six months into it. We’re getting lots of anecdotal information, which needs to be verified by large cohort, follow-up studies. When people recover, how soon until they get back to normal? You’re hearing about people who get sick, go to the hospital, come out, and then it takes weeks, if not months, for them to begin to even feel slightly normal. That’s the second thing. The other thing we want to know is what is the full extent of the clinical manifestations? We learn things every week, like this bizarre inflammatory syndrome, multi-inflammatory syndrome in children. That’s really important. MIS-C it’s called. And then, finally, what about therapy? Are we going to be able to get a good antiviral, the same way as you can essentially shut it off completely, so the second you get a diagnosis, you take a few pills, or you get an injection, and you’ve actually suppressed the virus? Those are the four areas that I really want to know about as we go forward.

31:25  

Minor: Returning to a point that we discussed earlier on public health and public health departments within communities, within states and the public health infrastructure across the country — you know, we are a nation founded on the principle of federalism where things are distributed between the federal government, states and then local communities. And yet, this virus doesn’t know the difference between one county or one state or indeed one country and another. You talked very passionately about reconstructing, rebuilding our public health infrastructure in the United States. How do we need to think about balancing the local public health departments, where the work is actually being done with people, and then a broader infrastructure related to public health at the state and national level?

32:14  

Fauci: Well, that’s the $64,000 question that’s being debated right now. And our response, you know, there’s arguments back and forth: Should the government, the federal government, provide resources, direction, guidance, and then pull back and let the states do it? Or should they direct it federally? You know, you can get arguments on both sides. Many of the states say, give us the resources; we’ll take care of it. Others say, tell us what to do, and we’ll do it. So we’re a big country. We have 50 states; we have 3,007 counties. So it really is an ongoing argument. And there are pros and cons of each approach. I mean there’s some advantage of a federally dictated and mandated approach. But there’s also advantages of a “delegating it to the states” approach. And to be honest with you, I don’t have a good, firm answer for you, except you’ve got to figure out on a case-by-case basis, what the best approach would be.

33:22  

Minor: Are there topics we haven’t covered or points you’d like to make today or would like us to keep in mind moving forward?

33:29  

Fauci: I just always make the point because I try to get it articulated as often as I possibly can: This is a bit of a confusing virus, because I’ve never seen one in which the protean manifestations are so extreme. You get 20% to 40% of the population that can be asymptomatic infection. They don’t even know they’re infected unless they get tested. Then you get some that get minor symptoms, moderate symptoms, severe symptoms, hospitalization and death. We’ve got to convince — because right now the people who are getting infected during the surge are young people about a decade and a half younger than the group that got infected in the first couple of months of the outbreak — we’ve got to convince them that just because they get infected, and the likelihood that they’re not going to get seriously ill, doesn’t mean that their infection is not a very important part of the propagation of the outbreak. So you’ve got to think not only out of your vacuum, and think of not only your personal responsibilities, but your societal responsibilities. Because although you may not get sick, almost certainly you’re going to infect somebody else, who almost certainly infects somebody else. And then you will get a vulnerable person who will be sick, who will go to the hospital, who might die. So the best way to reopen the country and to get back to normal is to be very prudent in protecting yourself from getting infected. That’s a difficult message when people don’t take something seriously, but we’ve got to hammer that home.

35:14  

Minor: Well, Dr. Fauci, thank you very much. And thank you to all who’ve joined us today for this fireside chat with Dr. Fauci. Be safe, be well and take care of yourself and take care of each other. Thank you.

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2023 ISSUE 3

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