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Coronavirus Infections—More Than Just the Common Cold

Educational Objective
To understand the latest developments in the spread and management of the 2019 novel coronavirus.
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From the JAMA Network, this is JAMA Author Interviews.  Conversations with authors exploring the latest clinical research, reviews, and opinion featured in JAMA. 

Howard Bauchner: Hello and welcome to this author interview and I'm told that we're also streaming live.  This is Howard Bauchner, Editor-in-Chief of JAMA, and I'm here with Tony Fauci, who is the director of National Institute of Allergy and Infectious Diseases of the NIH.  Welcome, Tony. 

Anthony Fauci: Good to be with you, Howard. 

HB: So, we're obviously here to talk about the coronavirus infections and, as many of you know who may be listening or will hear this a little later on, we were very fortunate.  Last Tuesday evening, Tony submitted an opinion piece to us, a Viewpoint.  Phil Fontanarosa and I quickly edited it, returned it to Tony on Wednesday morning.  He revised it quite quickly and then it was published on Thursday, which for us is about as quick as we can turn around an opinion piece.  The title of that Viewpoint was Coronavirus Infections-- More Than Just the Common Cold.  So, that was published on Thursday.  It is now Monday.  And actually we waited to do the podcast to see what would happen over the weekend through today.  So, Tony, before we get started updating our listeners, can you tell us a little bit about the coronavirus infection Viewpoint?  You talk about coronavirus and then you talk about SARS and MERS.  So, why don't you take the people who are listening or watching through what the Viewpoint talks about with respect to those two diseases. 

AF: Well, the Viewpoint really follows the title of the Viewpoint.  Coronavirus is not just the common cold.  And the reason I made that title is because I wanted the audience as they read the perspective to appreciate a few things.  First of all, when we think of coronaviruses historically prior to the year 2002, that they were a wide family of viruses that also infected animals, but four of the coronaviruses-- particularly the beta-coronaviruses-- account for about 10 to up to 30% of the common cold in any given winter season here in the United States as well as in places like Europe.  However, in 2002, that changed because the coronavirus jumped species from an animal reservoir and infected individuals from China at first, which then over a period of several months exploded into a global pandemic of about 8,000 cases and 774 deaths. 

And it really was a global pandemic and what it exemplified is what we talk about when we say that viruses emerge from animal reservoirs, adapt themselves to humans, and can sometimes cause considerable outbreaks.  Many times-- and I think the H5N1 bird flu and the H7N9 bird flu-- you can jump species from an animal to a human, but it is dead end at that first jump, so that a chicken can infect a human, but that human doesn't infect anybody else.  So, that is going nowhere.  That virus did not adapt itself very well to humans.  But the first time the coronavirus did that with SARS, they did it very, very well.  And the other lesson from that that we discussed in the Viewpoint was that good public health measures of identification, isolation, and contact tracing was able to put an end to the epidemic in a relatively timely fashion. 

And then fast-forward several years, everything was going along fine, and then in 2012 we had another species jump, again from an animal to a human.  Curiously, it was felt that SARS went from a bat to a palm civet to a human, and MERS apparently went from a bat to a camel to a human in the Middle East, hence the name Middle East Respiratory Syndrome.  That had about 2,400 cases and approximately 800 deaths.  So, take a look at those numbers for a second.  The mortality of SARS was about 9-10% and the mortality of MERS was about 35-36%.  And, again, it was taken care of, even though it still smolders in the Middle East, and then a few years later, yet again, another coronavirus-- this time the Wuhan 2019 novel coronavirus-- almost certainly jumped species from an animal reservoir to a human in China, infected a number of people, and now we're seeing-- interestingly and in an amazing way-- right before our eyes the evolution of what looks like is going to be a serious outbreak. 

And in China right now, as of this evening's report, there are over 2,900 cases and about 83 to 85 deaths.  The numbers literally change by the hour, so at any given time you'll probably have a slightly inaccurate number.  It has spread to all 30 provinces in China and it has gone to more than a dozen countries outside of China, mostly in Asia, but also in France and Germany and now here in the United States.  We have five cases.  One in Seattle, one in Chicago, one in Arizona, and two in California.  So, right now, when you have a travel-related case, that's, you know, in many respects concerning, but we handled it properly.  We did the standard public health measure of identification, isolation, and contact tracing.  Fortunately, there have not been secondary cases in the United States, but again, for the listeners of the program and for the people who will be looking at the podcast, I would not be surprised if there are several more travel-related cases and even a secondary case in the United States. 

So, it's an evolving problem that literally changes day by day and that's the reason why we take it very seriously. 

HB: Tony, just to go back, both to SARS and MERS.  So, SARS was a mortality risk of about 10%, MERS is higher at about 30%, this is now 83 of 2,910-- 

AF: It's about 3-4%. 

HB: Three or four percent.  How good are we at defining the denominator?  We're very good at the numerator, so the 774 deaths from SARS, but the 8,098 in the denominator.  How good are we at defining the denominator in these outbreaks? 

AF: Well, that is the critical question, Howard, and we are not very good at this point because whenever you have a respiratory infection like this, classically, you're going to have a spectrum of involvement.  And I am absolutely certain that there are a lot of people out there who have some mild cough, some myalgias, who are not bothered by it, who are going to work, who are just going about their normal business who don't get counted.  The only ones that are being counted is the one that present to a hospital for medical care.  Of those, about 25% of them have serious illness requiring respiratory support, oxygen, and possibly even intubation.  So, the answer to your question is that I am virtually certain, Howard, that the denominator is much, much larger.  Which means that the mortality rate is likely to be much less than the currently-established mortality rate. 

HB: Now, with SARS and MERS, as is often the case with respiratory disease, it's often the elderly and those with other morbid conditions.  Now, 83 deaths with the current coronavirus infection.  Is there a way of characterizing the 83 deaths or do we not know quite enough about them yet? 

AF: Well, we know something about them and the majority of them are in people from middle age to elderly.  The overwhelming majority of those that have died are either elderly and/or individuals with underlying conditions.  The virus can infect anyone at any age, but when you look at the demographic profile, it's clear that there are not a lot of children and not a lot of very young people who are infected.  Clearly, the majority, as I mentioned, are middle age to elderly. 

HB: And for the people who are infected and then develop respiratory symptoms, is there any data emerging largely from China?  Because from the other countries around the world the numbers are going to be quite small.  Is it mostly supportive treatment?  Are there any antivirals that people are trying? 

AF: Good question.  For the most part, it's pulmonary supportive therapy.  However, with SARS and MERS, there was anecdotal historical control data showing that a drug called Kaletra, which is a combination of two antiretroviral drugs, had some benefit in individuals with advanced disease.  But remember it was a historical control, so there's no solid evidence that it's beneficial, but it's being used on a compassionate basis.  In addition, the drug Remdesivir, which is a drug that we had been using without any great success in Ebola and was one of the four drugs in the clinical trial that were shown that two monoclonal antibody preparations were effective.  So, the answer to your question, Howard, is that there is the empiric compassionate use of some antiviral drugs without any proven benefit. 

The other possibility is that back in the days of SARS we developed monoclonal antibodies against SARS.  We never had to use them because by the time we developed them, the outbreak had been brought under control, but hopefully there will be some cross-reactivity between the SARS and the novel coronavirus.  Because if you look at the phylogenetic tree, the novel coronavirus is much closer to SARS than it is to MERS and there's somewhere between 75 and 90-plus percent homology between the two, so there should be some degree of cross-protection, we hope.  If not, we want to get some samples from people who have recovered so we can derive broadly-neutralizing antibodies against this virus that are very specific for this virus. 

HB: Now, Tony, I was struck by the initial reports that it seems like there was a diagnostic test readily available.  Am I misunderstanding it?  So, if someone arrives from China, has a fever, how quickly can they make the diagnosis of coronavirus infection? 

AF: They could do it pretty quickly within a period of overnight or a day or so.  It's a PCR reaction, Howard, and you know we've gotten so adept and advanced in PCR technology that they can make the diagnosis pretty quickly. 

HB: Now, I think people pick up the newspaper-- it's being covered on the front page of almost every newspaper in the United States-- and are following the stunning developments in China.  I mean to try to quarantine a city of 7 to 10 million and now kind of circle quarantine of 35 million.  Can you comment on that?  And I know there was an editorial in the New York Times by Howard Markel about whether this will be effective.  Can you just talk about that, Tony? 

AF: It is unprecedented.  They've not only shut out the traffic out of Wuhan-- planes, trucks, buses, ferries, rail-- but they've done it to a number of the surrounding cities.  Wuhan has a population of 11 million.  Some of the cities that most people have never heard of have populations of 5, 6, 7 million.  So, at least 35 million people are on lockdown.  There's no precedent for that.  There has been some downside in trying to essentially quarantine an entire city.  It was not successful when the officials in Monrovia tried to lock down the people with the Ebola outbreak.  It causes panic and it causes an interruption of supplies that people need.  However, the reason I'm not criticizing this, Howard, is that it's been never done on a scale like this and it could possibly work.

So, rather than say historically it doesn't do much good-- which is true-- I think it's important to wait and see that maybe the Chinese-- because of the state of their society, that they're able to do that.  I mean, as you well know, there's no chance in the world that we could do that to Chicago or to New York or to San Francisco, but they're doing it.  So, let's see what happens. 

HB: Oh, it would be a challenge in the United States.  That's for certain. 

AF: Right. 

HB: So, Tony, you've lived through SARS and you've lived through MERS.  If you had a crystal ball, what do you think the next few weeks will bring? 

AF: I think things are going to get worse before they get better and whether this turns into a global pandemic before it is something that becomes entrenched and we can't do anything about it.  If the Chinese can put their arms around, as it were, the outbreak in China and the countries that have travel-related cases handle it well enough so that it doesn't evolve into a sustained outbreak in their country, I think there's a possibility that it could be turned around the way SARS was turned around.  But it's going to be a real tightrope walk, Howard, because if it gets so expansive, then it's not going to just disappear the way SARS did.  So, I think the next 4 weeks to 5 weeks are going to be critical. 

It's either going to start peaking and go on a downturn or it's going to explode into a global outbreak. 

HB: Now, you mentioned there's-- I think five cases in the United States-- is that the number you used, Tony? 

AF: Yes, there is five cases. 

HB: So, I assume each of those individuals are in isolation. 

AF: That's the thing when I said that the system has worked.  Each of them were identified, isolated, put into isolation where they won't infect anyone.  The people who are caring for them have personal protective equipment.  And, importantly, their contacts are being traced.  I must say I am pleased that these people were not picked up by airport screening.  These people came into the country, knew they were from Wuhan and as soon as they started to feel ill, they presented themselves to the local health authorities who were astute enough to pick up that these people had traveled to Wuhan and every one of them has expeditiously gotten into isolation.  And I hope-- I hope-- that this means we're not going to see any secondary cases, at least from these individuals. 

HB: So, by secondary cases you mean in the contact tracing of those five individuals there will be no additional cases? 

AF: Exactly.  That they would not have transmitted it to another individual. 

HB: And how long do the people-- these five individuals-- have to stay in isolation? 

AF: They would have to stay in isolation until they stop shedding virus.  Because the one thing you don't want-- and we have no knowledge of this and it varies greatly from one infectious disease to another-- even if someone clinically is well, you don't want to put them out in society if they're shedding virus from their nasal secretions, from their feces or what have you. 

HB: And do you know if any of the five have needed ventilators or are receiving any of the antivirals you mentioned or have they generally been relatively healthy in isolation? 

AF: It's been a spectrum.  Some of them are more ill than others.  Some are doing quite well.  Some are requiring some added accelerated therapy. 

HB: You know, Tony, about a year, 18 months ago, you wrote a wonderful viewpoint for us about the ability to accelerate the development of vaccines.  It was extraordinary.  You showed this incredible table or figure that vaccine development, when it's emergent, has come down from 18 or 24 months down to 3 or 4 months.  If the cases in China spread and it does become a global epidemic, where would we be with vaccine development for this condition? 

AF: The Chinese, when they made the diagnosis and showed it was a coronavirus, they put the sequence up on a public database.  As you well know and as I mentioned in the article that I wrote as the viewpoint, today you don't need to get the virus in hand.  All you need is the sequence because the platforms that we use in vaccinology now are generally all gene-based or molecular biology recombinant DNA technology-based.  So, we partnered with a company called Moderna that specializes in messenger RNA platform.  We got the sequence.  The protein to which we want to make antibodies is the spike protein of the coronavirus.  We've taken that gene, but it in the appropriate plasmids into the mRNA and we're starting to make the vaccine.  We predict-- and I'm reasonably confident, there may be glitches, you know, you never can predict, but I'm reasonably confident that within 3 months or less we'll be in a phase one trial, which will break the record as the fastest one. 

Zika was 3.25 months.  I think we can do better than that here.  We're not the only ones that are developing a vaccine.  A number of companies using different platforms are already started on the development of a vaccine.  So, if phase one starts in 3 months, it'll take about 3 months to get safety and some immunogenicity data.  And then if you proceed to phase two, which we fully intend, then if you want to talk about on an emergent basis, if we do need this, if it does turn into a global outbreak, it will probably with emergency use take about a year before we can actually get a vaccine that is deployable as an intervention. 

HB: Tony, you lived through the emergence of HIV, numerous other remarkable and often times devastating infectious diseases.  What continues to surprise you? 

AF: Well, it used to surprise me, but since we've been through it so many times, Howard, it doesn't surprise me anymore.  It's that we've always had emerging infectious diseases.  We're experiencing them now and we always will have emerging infectious diseases.  And that is because what we have is the microbial world, we have the human species, we have animals to which viruses and other pathogens don't kill them off, they just reside in them as a reservoir, and that's how you get the outbreaks we have now.  Ebola, zoonotic.  Others, zoonotic.  Zika, zoonotic.  Now we're dealing with a new coronavirus.  So, it used to be a surprise how often this happens, but now it's just part of what happens in the interface between humans and the microbial world. 

HB: Is there something unique about the coronavirus that has allowed this jump? 

AF: No.  I don't think it's something unique about the coronavirus.  It's something unique about the customs of people who have such close contact with animals, particularly exotic animals.  So, let's quickly go through the three coronavirus outbreaks.  In China, where for feast days they sacrifice and eat exotic animals like palm civets and racoon dogs, bats are the primary reservoir.  They poop on or urinate on or what have you these animals or on food that's in the market.  People come and get close contact with, if not consuming, these exotic animals and there you go.  You have SARS.  MERS did the same thing.  The close interaction between the beloved camels and the people who take care of those camels. 

That's how you get the transmission from the bat to the camel to the human.  And now in the novel coronavirus, we don't know exactly what that animal was, but some animal, probably in a wet market where they bring in a variety of different types of wild game, and people sacrifice them, particularly around holidays like the lunar new year, it is totally not surprising that you're seeing the facilitation of this jump from the animal species to the human. 

HB: Well, I know you've done a lot of interviews today, Tony, so just one or two last questions.  The first is my sense is that we're better as a country and we're better as a planet in addressing these in a collaborative fashion.  Do you think that's true? 

AF: Oh, absolutely.  Absolutely.  We live in a global society and the global health security agenda, which is really trying to tie the different countries together, both in the ability to identify the communication, the sharing of specimens.  It's something that's much, much better than it was years ago.  Much less siloed. 

HB: And the last question.  Patients are likely to be anxious about this and may seek care with clinicians.  What should a clinician do? 

AF: You know, it's easy.  The CDC, as usual, is on top of things and they have a guide for clinicians who might come into contact with a patient like this.  You know, if somebody comes in-- and it's obviously difficult when you're in an influenza season, here we are in the end of January, the peak of the flu season.  You're going to get a lot of people that are going to be coming in with respiratory infections.  Right now, it behooves us all if someone presents with a respiratory pulmonary involvement and fever to just ask them a question.  Have you been in China recently?  And if so, you put a mask on the person, you put them in an isolation room, and you contact the CDC. 

HB: This is Howard Bauchner, Editor-in-Chief of JAMA, and I've been speaking with Tony Fauci, a good friend to JAMA and more importantly just a national treasure.  Tony knows how much I think of him and everything he's contributed over four or five decades to the health of people living both in the United States and around the world.  Tony is the Director of the National Institute of Allergy and Infectious Diseases.  Tony, I know it's been a busy day doing many interviews.  I can't thank you enough for spending the last half hour with me. 

AF: Very happy to do it, Howard.  Anytime. 

HB: Thanks so much for listening.  For more podcasts, visit us at jamanetworkaudio.com.  You can subscribe to our podcasts on Stitcher and Apple Podcasts. 


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