Diagnostic testing, NSAIDs, ACE Inhibitors, antivirals, and more. Anthony Fauci, MD from NIAID discusses latest developments in the spread and clinical management of COVID-19 and the SARS-CoV-2 virus with JAMA Editor Howard Bauchner, MD.
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From the JAMA Network, this is Conversations with Dr Bauchner- interviews featuring researchers and thinkers in health care about their publications in the latest issue of JAMA.
Howard Bauchner: Hello and welcome to this author interview. This is Howard Bauchner, Editor in Chief of JAMA. And once again, I'm joined by Tony Fauci, Director the National Institute of Allergy and Infectious Diseases. Welcome, Tony.
Anthony Fauci: Good to be with you, Howard.
HB: You've been at the NIH for 40 years, have you ever seen anything quite like this?
AF: No. I'd have to say, quite honestly, Howard, this is totally unique. I mean we've been through emerging infectious diseases, experiences, and in some cases, crises, like we had with the anthrax scare back in 2001, the early years of HIV, the scares of the pre-pandemic H5N1, H7N9, the uncertainty of the 2009 H1N1 swine flu, but nothing of the magnitude of this because those things, many of them evolved slowly, as with HIV, even though it turned out ultimately to be a terrible -- you know, affront of the human civilization with a lot of suffering and death; ultimately, it was over many, many years. Many of the other threats never really materialized.
Ebola, although there was a lot of concern about it, there was never really any serious concern that it was going to be a widespread outbreak in the United States, although it devastated -- in some respects -- several African countries, particularly the West African countries early on. But to have a situation now, we have the evolution of an outbreak that clearly we know what it can do. We've seen what happened in China. We see what is currently happening in the European countries, particularly Italy, and France, and other European countries, and we know it's right now here in the United States. It shouldn't think panic us or frighten us, but we really need to realize that we're dealing with a serious problem that we have to address and we have to address it in a very bold way, which I think you're starting to see both from the federal government, the state, and local, as well as individuals are right now mobilizing to try and address this emerging threat, which is really quite serious.
HB: I saw just a change in the resolve of the U.S. last week, and I think it followed what was occurring in Washington State, and then the reports from Italy, which were so enormously concerning. So, I sense both resolve but I do sense panic, and I'm just wondering if -- what's your sense of that?
AF: Well -- you know, obviously, when the general public, who is certainly not used to thinking about or even needing to address something like this, there is -- in many respects -- something -- it varies between person and person, but it's something that, in some individuals, borders on panic because there's the uncertainty, they do not know where it is going. So, what I try to do when I talk to people publicly, as well as privately, is channel the energy associated with what might be panic towards the resolve to do something about it. I mean obviously, panic is an understandably human feeling, reaction, emotion, try to -- best as you can -- at every level to put that aside and say, there's a lot of energy in that, let's get that energy and apply it to doing the things that we know can actually mitigate this.
And I think the case in point, Howard, is looking at the recommendations, which came out a couple of days ago about mitigation, things that might have appeared then, and even to some people now, as really a bit of an inconvenience. Why do you want to stay away from bars, and restaurants, and sporting events? Why do you want to cancel gatherings? Why are you telling all the old people and the people with conditions to essentially isolate themselves in their own homes, there is a really good public health reason to do that. And I want to appeal specifically to the people who are the younger group who feel, understandably, -- I -- you know, I'm thinking back when I was in my 20s and 30s, I had the feeling that's understandable, but unreasonable that I'm invulnerable. And because they see the statistics show that, in general, younger people do really very well. The overwhelming, the majority of them do fine, they get an illness that can be mild, they recover, and they're fine.
But they have a responsibility in society to protect themselves, not only because there is a possibility, they could have a serious consequence, but as important is that they may be the vectors of the infection that could continue its spread. I had a phone call just this morning, the WHO phone call where the WHO group essentially gets dozens and dozens of people from throughout the world on the phone to relate their experiences and to learn from each other. And in the conversation was people from Italy, and France, and others who had visited saying, almost pleading, with the rest of the world to please take this very seriously because it happens all of a sudden very abruptly. You have some cases -- there not a lot of cases, and then all of a sudden, boom, it starts to skyrocket. And the best time to mitigate is before that happens because if you wait until after it happens, you're playing catch-up.
And catch up doesn't work very well with this outbreak.
HB: I have been incredibly impressed just the last 6, 7 days, the resolve at many hospitals and academic medical centers to really expand their capacity, if necessary. So, once again, sensitivity of testing early in the disease. Any newer data? You know, is it above 90% early in the disease? Is it higher? Where are we on testing and sensitivity?
AF: You know, when you say early in the disease, let's get sort of really specific so people will know what we're talking about, Howard.
AF: I'm saying, if an individual gets exposed, somebody coughs on me right now, who is -- clearly has coronavirus disease, and the virus enters into my nasal pharyngeal space, and perhaps into my lung, how long is it going to take for me to turn positive? First of all, we don't know the answer to that. We can surmise it, I think, reasonably so. And say, well, the virus would stop replicating to the point where you get some symptoms at a median of about 5 days, the range being 2 to 14. So, again, I don't have a clinical study proving anything, but I can say, it's not going to happen immediately. I think if somebody coughs on me now and then I go down to the -- wherever it is that does the testing, and I get a test, I'm going to be negative. I mean I'm almost sure I'll be negative. Maybe in 2 days, which is the lower limit of the bracket of the incubation period, you might start to turn positive then.
When you get to the point where you're symptomatic, you almost always are positive. So, I think it's in that bracket between a couple of days from exposure to the time which is the median time. And, Howard, let me caution our viewers and listeners that, that this is just an extrapolation, and this isn't solid data that we've done a major study to do this.
HB: Yeah. I think what's so unique about you, Tony, is you're very, very willing to say there's unknown and move on. So, let's go to some of the other questions crossing my desk every day. Quite a bit of concern about nonsteroidals, there was a tweet by someone in France based upon a letter in another journal that didn't have a lot of data. Any sense about nonsteroidals and people avoiding them, if they're developing symptoms? Should they switch to acetaminophen? Or just not enough data to know?
AF: Well, first of all, there's not enough data in any event positively or negatively. What I suspect happened, Howard, there was -- you know, sometimes discussions off the cuff turn into letters, turn into social media, turn into a lot of discussion, and you have no idea where it comes from. What I think likely happened was that people were thinking, well, you know, with influenza, in children, if you take aspirin, you can possibly get Reye's syndrome, which, as we know, is a neurological disease and syndrome mostly in children. And then I think somebody made the leap from that to say, well, you know, if you give anti-inflammatories, you give nonsteroidals, it may be the same thing. Well, most nonsteroidals -- not most -- non-aspirin nonsteroidals are not aspirin, number one. And it depends on what you want to use the nonsteroidal for. If you really want to just bring the temperature down, I mean Tylenol will every 6 hours is the way to go, as we all know, as physicians.
Bottom line is, I have not seen any firm data to indicate there's a problem or to prove that there's not a problem.
HB: Another clinical issue that really come up the last few days is this issue about ACE and ARBs in individuals who are either on them or develop disease. Now the Heart Failure Society of America, ACC, and AHA just came out with a statement yesterday. I don't know how familiar you are with the question, Tony, but I'll let you comment.
AF: Well, I am quite familiar with the question. So, here's the issue -- and this is something that I take a little bit more seriously about we really need to get data and we need to get data fast, Howard, and here's the reason why. If you look at the mechanistic rationale for concern, it's there and it's -- and it's firm, and that is, that when you give an ACE inhibitor or an ACE inhibitor can result -- I say can -- can result in an increased expression of the receptor for ACE. So, what is possible is that people who are on ACE inhibitors, a very commonly used drug for hypertension, that they may be, without knowing it, increasing the expression of receptors for the virus, itself.
That's an extrapolation, that's not based on known data, but it is a possibility that we need to address. I was struck by something that I read just early this morning, Howard, there was an article -- I think Bloomberg published it from a medical summary that in -- I believe it was Italy or in Europe, but I think it was in Italy, that 99% of the people who died had an underlying condition, that's not surprising. However, when they broke down the underlying conditions, 75% of it was hypertension, which was, to me, a bit of a red flag, because Italy is a very developed country. And I would imagine, if you knew the patient had hypertension, then the patient, almost certainly, had a physician.
And that physician almost certainly treated the person for their hypertension. So, if you could imagine -- and again, this is just my putting some dots together, Howard. This is no data, I'm just -- you know, giving you right off the top of my head. If 75% of those so-called underlying conditions was hypertension, and the hypertension was well-controlled, why should someone who has hypertension that's well controlled have a much greater chance of dying than somebody else with any other kind of underlying condition? I mean I look upon someone who has well-controlled hypertension and nothing else wrong with them as a reasonably healthy person, yet it was skewed towards people with hypertension, which tells me I don't know what the answer is, but somebody better look really carefully and that's what we're hopefully going to get that data from the Italian scientists.
When they did the natural history data, is there any way they could find out what drugs those individuals were on? It may turn out to be absolutely nothing, but I think we need to at least look at it.
HB: Tony, many questions, so let's just go through them. Anything new on children? You know, we've talked about this before. It's clear that they get disease. On rare occasions, they get serious disease, but it still appears as though the mortality rate, the amount of serious disease in children is very small.
AF: That is still correct, no doubt. If you look at the demographic profiles of the cases from the countries where there is a lot of experience, China, South Korea, now accumulating experience in the European countries, it looks like that data hold true. But as we know in biology and medicine, it's never 100% but clearly, the rather strong bulk of the data indicate that children do quite well when they get infected.
HB: Similar to last time, respiratory spread versus droplets. And then the question about, how safe are all the packages that people are now getting delivered to their homes?
AF: Well, there was a paper that came out a couple of days ago from Vincent Munster, he's at the Rocky Mountain Laboratories here at NIAID in Hamilton, Montana. And he did a study where he looked at the viability, namely, the ability to culture virus on a variety of surfaces, as well as how long it lasts in an aerosol form, aerosol being that the droplet which suspends the virus is around 5 microns. And so, it can stay in the air for several minutes before immediately dropping to the floor where a larger droplet would essentially fall right down to whatever surface it is. But getting back to the volubility of the virus on surfaces, they compared stainless steel, cloth, polypropylene, etcetera, etcetera.
And if you look at the data, it goes rather substantially down probably to a level that is detectable, but so low that it may not have clinical impact, in most cases, by 36 to 48 hours. So, I think you'd have to assume though we don't know because even though you can detect it, it may be a dose-response situation, but it looks like that up to 2 days on these surfaces. Having said that, you would imagine that if somebody puts something in a crate in Shanghai, and gets it on a boat, and sends it to Seattle or San Francisco, that by the time it gets there, that there is no viable virus. So, in that regard I think that an inanimate object that comes from a place where there's a high degree of infection is much different than a doorknob where somebody sneezes in their hand, opens the door, and you come there 5 minutes later.
I mean that's the reason why there's recommendations, to the extent that you possibly can, to essentially wipe off surfaces that are frequently used communally by a lot of people.
HB: Every few days, a new therapy emerges. I know my intensive care unit colleagues are concerned that the use of varying therapies may make it really difficult to hone in on effective treatments. So, the one that people have been focused on the last few days is hydroxychloroquine. Any sense of what's happening with that?
AF: Well, yeah. What I think is going to happen, Howard, I think that there's so much out there on social media and even in medical letters, particularly unreviewed reports, that people are going to just start using that anyway. So, hopefully, we'll be able to put a program where you could make it accessible to people at the same time as you're studying it, but that's in active discussion. No decisions have been made yet about that, but I would imagine the more people read about that, the more likely they would want to just try it empirically.
HB: Protecting the elderly and protecting healthcare workers is critical to the future ability to provide care. Lots of concerns about healthcare workers, who to test, who not to test, when they can return to work. Any evolving issues? I know the CDC just released some new recommendations, although less focused on healthcare workers and more on the general populace.
AF: Yeah, I mean the recommendations that we rolled out 2 days ago and discussed yesterday at the press conference at the White House, the issue that I think is important that we're going to be facing because I believe -- I got off the phone this morning early with some of our colleagues from New York City, and it involves sort of like almost a Sophie's Choice where you're going to need personal protective equipment to do testing, so you could protect a person who sticks that swab into your nasal pharynx and you start coughing up. But you also need PPEs for the actual healthcare providers who are taking care of patients. And I think a supply issue is going to be something that's front and center in discussions and concern. Do we have enough equipment? And if not, how do we get it? So, that you can both protect the people who might be administering the test, as well as those who are taking care of patients.
I think the issue, Howard, of the drive in, walk in facilities, which are now starting to stand up -- as of the announcement from the FDA, and the CDC, and ASPD yesterday that, in fact, that might sort of mollify the problem a little bit because if you give somebody a swab and you ask them to essentially swab themselves and put it in the appropriate vehicle and give it, you can sort of get away from the need of PPE because the person is alone by themselves doing that. But the issue of the distribution of PPEs is going to be one that really needs to be addressed.
HB: For the healthcare worker who ultimately tests positive, is there 2 negatives before they can come back? Is it 7 days and they are symptom free? Is there a final decision on that recommendation?
AF: Well, Howard, that is an evolving story for the following reason; when you have a couple of healthcare workers who get infected, you say obviously the perfect thing to do is they recover from the symptomatology and they have 2 negative swabs separated by 24 hours. We are approaching a point where you're going to get enough people who are infected, you're going to have to look at that, and say, we don't even have the ability to do that. We're going to have to -- by good judgment -- make a decision about how many days post-alleviation of symptoms can they go back to work? Otherwise, we're going to be not having enough healthcare workers to go back into the field and do that. So, I would say, Howard, it's an evolving situation. And if we get into a situation -- for example, New York is already in a situation where they're really having difficulty about making these hard decisions.
HB: Tony, there's still a number of antivirals that are being used by intensivists, but there are also some that are under study. Any new emerging data about the antivirals and the different specific antivirals?
AF: Well, you know, the answer is no, but I hope that we'll get it soon. You know, as I mentioned on a previous podcast, Howard, the Chinese have two studies that are ongoing, one is for advanced coronavirus disease, and the other is for early coronavirus disease. And I believe its powered to about 4- to 500 patients per. One of the study with advanced disease has a bit between 200 and 300 individuals so far; they're having a difficulty enrolling people now, it's a randomized trial because people want to get the drug and don't -- you know, they don't want to be in the trial, they want to just get the durg. What I think would be important is if the Chinese Data and Safety Monitoring Board can take a really close look at the data and see if there's any hint of anything, either efficacy, and or -- and hopefully not -- any adverse events because we desperately need the data because, as the word gets out, sometimes based on very little data and only anecdote that these things work, whether it's Kaletra, or remdisivir
We've got to be able to determine if they work, and if they're safe, and that's going to be really a challenge as the weeks unfold and cases increase.
HB: We know the Seattle area has struggled. There's been some hospitals in the Bay Area that have really struggled with the number of cases. Obviously, my hometown of Boston, just the last two or three days. And then, I think for many reasons, people are concerned about New York, the density of the population. Although I think the intensive care units are continuing to do generally well. Do you have a sense -- we really started much more stricter social distancing a few days ago, I would say late last week, over the weekend thanks to you and your comments publicly about the need to do that. And I think people became enormously concerned about data from Italy and from Seattle. The incubation period is about 2 weeks, give or take a few days. My sense is that by April 1, early April, we'll really have a sense if we can manage in terms of serious illness.
We still may not know that much about seroprevalence in the community and you commented on that yesterday in the press conference. But my sense is, other than that those four locales, most of the metropolitan areas are doing reasonably well with intensive care unit beds and that by April 1, early April, we'll have a better sense about how this is going to go. But I know you don't like to put specific dates or numbers on it, but what is your sense of what the next two or three weeks are going to tell us?
AF: I think you're right, Howard, we're going to know, for better or worse, whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice because if you look at the cases every day, and look at a very important number, how many of the cases are new. You know, as of last night, there was 900 and something new. Yesterday, there was 700 new. The day before, there was 500 new. If that continues to accelerate and within that group, there will be people who have serious disease that need intensive care, you're right. Pretty soon, in a matter of a week or two, I guess it's the 18th of March right now. You know, 12 days from now, 13 days from now is about your timeframe of 2 weeks, I think we will get a feel for whether or not we really do have enough of the supplies that it takes. I might mention, Howard, that there are the supplies that are out there, and then there's the Strategic National Stockpile, which has a lot of stuff in it, but -- you know, you need to backfill that as quickly as you can, once you start drawing from the Strategic National Stockpile.
HB: Tony some questions have come across my desk about equity, and health equity, and who's going to have supplies, and who won't have supplies? New York is a case in point. You have really well-endowed institutions, Columbia, Cornell, Mount Sinai, and then you have the public hospital system, which may not have the same resources. How does the City of New York, how does medicine -- the house of medicine think about that issue?
AF: You know, it's really a tough situation and I think it's going to require a group of people who bring in perspectives from all different components of society. You want to talk about what the physician scientists feel, what the person in the street, the general citizen, what ethicists feel. And you really got to sit down and hash it out about what the most appropriate thing to do is. It's a very, very difficult situation. If we ever get to that point, we will have to make a decision, who gets something, and who does not get something. That creates a considerable amount of ethical stress and ethical dilemmas. So, it's not something that any one person or any one organization can decide by themselves. You really have to get representation of broad components of society in that.
HB: Is there anything more that local, state, and federal government must do?
AF: Well -- you know, obviously, we all need to realize that it is really all hands on deck here. None of this can be taken as a matter of casual issues. And I refer specifically to people taking a really good look at the guidelines that were published on coronavirus.gov or CDC.gov, take a look at them. And to the best of your ability, try and stick by it. I know it's inconvenient for some. I know some people may disagree with it, but it's really based on an appreciation of what is going on in other countries.
HB: So, one other point, and one other question, then I'm done. Firstly, Bob Harrington is a graduate of Holy Cross, you couldn't make him prouder. And he says, all of the Holy Cross alums are incredibly proud of you. But, Tony, a different question. You grew up in Brooklyn, but you're a New York Yankee fan. Now, Tony, I'm a New Jersey guy and I ended up being a San Francisco Giant fan because my brother used to root for the New York Giants. How did you end up as a New York Yankee fan?
AF: Well, for those who know back then, in the late 40s, early 50s, when New York City had three teams, they had the New York Giants, the New York Yankees, and the Brooklyn Dodgers. And as strange as it seems, in Brooklyn, there was about 60% Brooklyn Dodger fans and literally about 40% New York Yankee fans. The interesting thing is that very few people were New York Giant fans, except the people who lived in the Bronx and lived in upper Manhattan. But it is not unusual, I'm not an outlier. There were many, many of my friends. You know, the comparison between Mickey Mantle and Duke Snider, the comparison between Joe Collins and Gil Hodges, and Pee Wee Reese and Phil Rizzuto, I mean the arguments we used to have in the candy stores used to be incredible.
HB: As I said, I grew up a Giant fan, and I was doing well until my mother threw away all my baseball cards, it was so painful, I had all those rookie cards. All right, Tony, there's other questions. I really want to let you go. Stay healthy, stay safe, you're a national treasure.
This is Howard Bauchner, Editor in Chief of JAMA. I've had the great privilege once again of talking with Tony Fauci, Institute Director, National Institute of Allergy and Infectious Diseases. Tony, thanks again.
AF: Good to be with you, Howard, always.
HB: Be well.
AF: You too.
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