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CDC Telebriefing Transcript

SARS: Genetic Sequencing of Coronavirus

April 14, 2003

DR. GERBERDING: On March 14, CDC activated the Emergency Operation Center to initiate the coordination of the SARS outbreak investigation. It's now April 14, and so we are entering into our second month of this operation, with a mixed picture, I would say.

Today we are aware of almost 3,000 cases of SARS that have been diagnosed in the world, including 193 suspected cases that are under investigation in the United States. The pattern of the global epidemic is mixed. We hear reports from Hong Kong, probably China, and certainly Singapore that there is ongoing transmission that the containment procedures have not adequately contained spread to the immediate group.

And yet in other parts of the world, including Taiwan and the United States and Canada, it does look like the outbreak has been contained, and that so far we are seeing very limited transmission outside of travelers to the affected areas.

One of the really important messages that we're emphasizing to the public health community today is that despite the fact that we do seem to be able to contain the spread of this disease in the United States and are not right now experiencing a situation that looks like the patterns in Hong Kong, we have to remain vigilant, because it is only one highly-transmissible patient that can infect a very large number of people.

And so even though we would like to be able to take a deep breath and relax a little bit here, this is absolutely the wrong time to do that. We must continue to identify suspect cases, to isolate individuals as quickly as we can and to do everything possible to prevent the spread of this illness into our community, so that we don't end up with an epidemic that is as rapidly progressive as we are seeing in some parts of Asia.

We have some very exciting news today from CDC related to the coronavirus itself. The sequence of the coronavirus was published over the weekend by the investigators in Canada, British Columbia. And they deserve an enormous congratulations for their efforts in getting it out as quickly as they did.

And today CDC has followed suit and has published a sequence of the virus we've been working with on our Internet site. We can now say with a great deal of confidence that the virus sequence at CDC is very similar to the virus sequence in Canada, with a difference of about ten based pairs, which is a trivial difference in a virus that's about 29,000 based pairs. And the virus here at CDC has an additional element at one end of the virus that we were able to add to the published sequence.

But this clearly is consistent with a brand new virus in the family of coronaviruses. And unfortunately the clues from comparing it to the animal viruses have not given us any real leads in terms of where did it come from. We can't say it's a mouse virus or a pig virus, or any other animal virus, necessarily, because it just isn't similar enough to the known species to be able to draw those conclusions.

But having this information is critically important for developing even faster diagnostic tests, and certainly should help us in the development of antivirals and vaccine work down the road.

So this is tremendously exciting.

As I said, we are basically 31 days into this investigation, and the fact that we have international collaborators, who not only identified the likely cause of SARS, but also have sequenced the virus and have created a number of laboratory tests that look increasingly promising.

It's a scientific achievement that I don't think has ever been paralleled in our history. So we are all collectively proud of the efforts of the collaborating investigators, and certainly at CDC with Dr. Larry Anderson, who is here with me today and his laboratory group, who worked on the virus and the sequencing here, as well as Tom Ksiazek, and many, many other scientists at CDC, who have been absolutely instrumental in contributing to the global effort.

So let me stop now and take some questions. I can get the callers on the phone wound up and I'll take a question from the floor, here.

MODERATOR: Ladies and gentlemen, if you wish to ask a question, please press the '1' on your touchtone phone. You will hear a tone indicating your line has been placed in queue, and you may remove yourself from queue at any time.

QUESTION: [Inaudible] --The U.S. Army has a [inaudible] antiviral compounds that are available plus the pharmaceutical companies through some efforts on Secretary Thompson's part, donated, or giving us things that they have on the shelf or in the pipeline, so the Army is rapidly putting those compounds through a testing protocol. So far we've had discouraging results for Ribavirin, which doesn't look like, at least in the test model, as having much activity against the virus. Although we don't know for sure it won't have activity in patients. But they are looking at all sorts of other things. And if we get a lead, we'll let you know. But so far we haven't got information that's really pointing in the direction just yet.

Let me take a phone question, please.

MODERATOR: We have a question from the line of Miriam Falco from CNN. Please go ahead.

QUESTION: Hi, Dr. Gerberding. I have two questions. Number one, do you know of any of the sequencing came from the specimen from any super-spreaders? And also what advances have been made in animal models and what difference does it make, now that you have the genome for the animal models that you were trying to develop?

DR. GERBERDING: Thank you.

I cannot tell you specifically which patients the virus came from, and whether or not that individual would be classified as a super-spreader. But we can check on that for you. The U.S. is dealing with a virus that was isolated from the patient tissues that we had here, and those patients came from Asia. And I believe that the Canadians were sequencing the virus that came from one of the Canadian patients. But we can go back and check on that in detail, and Tom Skinner from out Public Affairs Office can give you that information.

With respect to the animal models, a great deal of progress has been made. And we are waiting for the final reports from our collaborators in the Netherlands, who are working very hard on the primate model. But the virus has been put in a number of animal tissues, and we're hopeful that one of these will not only create a disease that would allow it to fulfill the conditions for saying that coronavirus is definitely the cause, but also be a model in which we could test antiviral drug treatments or other therapies.

So we're working fast, but we're not quite there with an announcement yet.

Yes?

QUESTION: The last time we had a news conference, you said it could possibly a year or so before we could see a vaccine for this. With discovering the sequencing now, do you see that timetable speeding up?

DR. GERBERDING: I would like to say that it would speed up, but unfortunately, there just is a finite amount of time to get a vaccine together. When you do have vaccine, the first step is to get an animal model where you can show that any virus component will create an immune response that can protect the animal. Once you have a candidate and an animal model, you still have to create the product in a safe format for people, and then at least go through the clinical studies to show that it's safe.

In order to get it licensed, you at least have to show efficacy in two separate animal models. That's just going to take some time, and I think it would be naive to say that we would have it in under a year.

Question from the phone.

OPERATOR: We have a question from the line of Rob Stein at the Washington Post. Please go ahead.

QUESTION: Hi, Dr. Gerberding, thanks for doing this. Two questions. The first one was: of the new cases that you've reported, I guess, from over the weekend--it looks like there's about 27--are any of them secondary transmissions involving family members or health care workers or anyone else, and if they are, what can you tell us about them?

And then the second question was: can you tell me what's being in hospitals to prevent--in this country to prevent outbreaks from occurring here?

DR. GERBERDING: Yes. Let me answer your first question, and that deals with are any of the cases that are new on the list cases of transmission to family members or health care personnel?

All together, of the 193 patients that we are investigating in the U.S. right now, 15 of them involve transmission to family contacts or other members in the family. Some of these did come in over the weekend. As I have said several times, we are casting a very wide net with SARS in the U.S., and so any person who has traveled and has any kind of fever or respiratory symptom has been on our suspected case list. So likewise, if family members have even a subtle clinical presentation, they get added to the list so that they can be isolated and evaluated. So right now we're at 15 members in that group, and all together five health care workers have been included in the suspected case list.

In terms of what we're doing to protect health care workers throughout the entire delivery system, the principle is that patients suspected of SARS are put in isolation. They're put in rooms that have the appropriate air exchange, so that if there is any tendency for airborne transmission, that we are minimizing it. In addition, the health care personnel and visitors wear masks, not just surgical masks under these conditions, but the N95 respirator mask, which is the appropriate mask for hospital environments where you're worried about airborne transmission.

In addition, of course, they are taking measures to avoid droplet, splatter and hand-to-hand or hand-to-surface contamination. So we call that standard precautions, but what it really means is use barriers and hand hygiene so that you don't contaminate yourself and then move the virus either to yourself or to another patient in the vicinity.

These are standard infection control precautions that have been used for a variety of infectious disease such as tuberculosis or many other infections, and I think the health care environment has a long tradition of familiarity with them. That may be one of the reasons why we have had a little more success with containment here, is because we have been using these standards for many, many other infectious diseases for a long period of time, and we're trained to know how to use them.

Let me take another question from the phone, please.

OPERATOR: Have a question from the line of Richard Knox with NPR. Please go ahead.

DR. GERBERDING: I'm sorry. We have a bad connection. We can't understand you.

QUESTION: Can you hear me?

DR. GERBERDING: Yes, we can.

QUESTION: Hi. This is Richard Knox from National Public Radio. Thanks very much.

Over the weekend we heard about a case of work--i wouldn't even call it work place, but transmission from one businessman to another at Heathrow Airport. The transmitted was apparently this fellow who took 7 Lufthansa flights around Europe. And I wondered whether anything more can be said about the investigation of the Florida case involving a woman who returned from China and a suspected co-worker?

DR. GERBERDING: We don't have any additional information on either of the situations that you've mentioned, but I just want to emphasize again that these are suspected situations in the U.S., and we are not able to say definitively that any of the people implicated in these chains(?) actually have SARS.

One of the steps that we will be taking this week in conjunction with WHO is to begin to distinguish which patients in the U.S. are probably SARS cases as opposed to simply suspected SARS cases. This is so that our information will be consistent with the way that WHO is reporting that data. And when we make that transmission, what you're going to see is a reduction in the number of cases that we are reporting as SARS in the WHO list, because they have a more stringent definition than we do, and many of the people that we're counting are not going to meet the WHO case definition. We're still going to follow them. We're still going to treat them the same that we have since the beginning here, because we want to err on the side of caution and isolate anybody who might possibly be in this category. But I'm just warning you to anticipate some potentially confusing changes in the way our numbers look, and we'll be reminding you about why we're doing this and what it all means in Thursday's MMWR.

QUESTION: Could I just ask a follow up?

DR. GERBERDING: Question up here.

QUESTION: Thanks for doing this. Some health care--some health authorities in Hong Kong are expressing concern that because they are seeing a wider clinical presentation, a wider range of symptoms among some patients there, their concern is they fear that the virus may have mutated. I'm wondering whether you could tell us, have you heard in the various cases that the CDC is tracking whether--have you heard of a wide clinical spectrum, and/or is there anything that you see in the sequence that would suggest whether this is a rapidly changing virus or something that looks pretty stable?

DR. GERBERDING: Well, let me first talk about the variability and what we're seeing from a clinical perspective in SARS. I'm an infectious disease doctor, and there isn't an infectious disease I know of where there isn't a highly variable clinical picture all the way from asymptomatic or mild disease to sometimes very severe disease.

So the patterns are not at all concerning for anything other than the biology of a virus and the variable biology of the people who have it. So that in and of itself is not concerning.

We know from almost the beginning of at least epidemiology that we've been able to track in Hong Kong, that there were some people who seemed to be highly efficient at transmitting, and others who didn't seem to pass it along to anybody. That's the pattern that we saw several weeks ago, and it's a pattern that we're still seeing today. So that again, in and of itself, does not imply anything evolving in the virus. It just tells us that it has a highly variable nature, and we wish we knew why that pattern existed.

On the other hand, this is an RNA virus. It's a single-stranded RNA virus, and that means there's just a single piece of the genetic material, and when you have that kind of virus composition as it reproduces itself, it doesn't have the zipper on the other side to match up perfectly, so it makes mistakes, and there's just a natural tendency for RNA viruses to evolve. The HIV virus is an RNA virus that does that too, as it each time it replicates, it might make a few mistakes, and so it is not surprising that we see strains emerge over time. We haven't documented that yet with this virus, and I think the fact that the sequenced data from the isolate characterized in Canada and the U.S. are so close, suggests that large mutations are not occurring. Perhaps there is some strain evolution that might account for the very minor differences in the isolates that we've looked at so far.

So in the short run, no strong epidemiologic or scientific evidence of mutation, but it's biologically plausible, and we'll be keeping our eye on these strains as we go forward.

There's a question here.

QUESTION: Thank you, doctor. Can you tell us where some of these news cases are popping up, if they're concentrated in any one area, or if they're just spread out across the country?

DR. GERBERDING: If you're speaking of the U.S. cases, it's just the same pattern that we've been seeing all along because the lead risk factor here is travel to Asia, and people travel to Asia all over the country. It's a very sporadic pattern of spread, and the most cases are in California and New York because the most travelers to Asia are typically from California and New York. Let me take a phone question, please.

OPERATOR: Laurie Garrett with Newsday. Your line is open.

QUESTION: Thank you. A quick question regarding the individual who turned up in South Africa, and the questions about the possibility that individuals who have a underlying immune compromise situation might either be more likely to get infected and have a [inaudible] illness or more likely to be a super spreader. So two parts to this question.

One: do we know anything about any of the super spreaders that could tell us whether or not any of them have any underlying autoimmunity or immune system suppression or have undergone cancer therapy, chemotherapy, anything like that.

And number two: what generally would you say are your concerns about the possibility of HIV finding its place in sub-Saharan Africa?

DR. GERBERDING: Let me speak to this issue of super spreaders. This is a term that we have used because it creates a plausible explanation for the pattern of epidemiology that we're seeing, but it still is really speculation. We don't know whether the virus is associated with a lot of spread in an individual cluster because of something having to do with the infected person or if it has to do with the type of containment or failure of the containment procedures that are present there.

So we need to understand the whole picture, why are some clusters expanding so rapidly and other clusters are extinguished or die out?

We do know that the clusters that are associated with the largest degree of transmission occur in people with the full-blown pneumonia, and usually very sick people. It's possible that they have higher titers or are crossing more or have more efficient air transmission of the virus, but all of these things are speculation right now. We're very eager to know and some of the clinical studies that are in progress in Hong Kong or elsewhere will help us get to the bottom of it, but it's no firm clues yet.

In terms of the pattern of spread in the African continent or elsewhere, given what we've learned from HIV and the incredible speed with which viruses can evolve in a given geographic area, of course we're very concerned as the virus enters any new population. Right now we don't have any information to say that if you are immunosuppressed or have HIV infection, that you are a better spreader or you get sicker, but I would at least be concerned about the possibility of more severe illness in people who are immunosuppressed. That just makes biological sense.

As we get more experience, again, with the full spectrum of illness--and by the way our tests will help us with this because when we have an accurate diagnostic test, then we'll be able to say, "This person really has it and it's mild. This person has it and it's severe." It will give us a gold standard so that we can compare apples to apples and oranges to oranges.

There's a lot to learn about the clinical patterns here, and we continue to work very aggressively as part of the WHO's collaborating team in various parts of the world to get this information together and get it back out to the clinicians.

Can I take one more question from the telephone, please?

MODERATOR: Geraldine Reyerson Cruz from Bloomberg News, your line is open.

QUESTION: Hello. Thank you.

Two things. One is I noticed that you were calling the strain for your research the Urbani strain. And I'm wondering about the naming of this. Is this distinct? Is this something that you're going to continue to use?

And also, secondly, in the bigger picture, what will success look like in terms of containment?

DR. GERBERDING: When CDC published its first New England Journal paper, describing the virology of this illness, we did propose the name of the Urbani virus to honor the fact that Dr. Urbani, who is our colleague and friend, who died of this illness and had done so much to really help define the early stages of the epidemic, that was the proposal.

But in fact, the names of all infectious disease agents are not picked by CDC or WHO. There's actually an international committee that has responsibility for choosing the names of all the organisms. So they'll get input from a lot of people, and I'm sure they'll be thinking about what's the best and fairest name for this illness, as they look at all of the options in front of them.

I forgot your second question. Are you still there? Oh, I think the question was: What's a good outcome, or what would really be the best-case scenario here for the whole SARS epidemic? I think the best-case scenario would be that we would see the virus go away. And that's not totally implausible as we enter the summer months in at least the northern hemisphere. But it would be, I think, unrealistic to count on that.

And that's why our efforts to identify a treatment and ultimately a vaccine still has to take such a high priority. We are very confident that we'll make progress in that regard, but it's a question of whether or not the science and our speed of being able to create those new products is fast enough to keep up with what has so far been a pretty rapidly emerging viral infection.

Question here?

QUESTION: Yes, Dr. Gerberding. And I apologize if I'm repeating myself. I got here a little late, from WFC.

What is it that you want the public to know about the announcement from the Canadian scientists about the cracking of the code? You know, should people expect the vaccine by the end of the week? Or what is it that you want the public to know?

DR. GERBERDING: Sequencing the virus is a major scientific achievement, and the fact that's it's been done so fast and so collaboratively is unprecedented in the history of science. But it is not the magic bullet for dealing with SARS. We've got a lot of work to do to fine treatment, and we've got a long road ahead of us in terms of getting an effective vaccine.

It's a necessary step, but it is by no means sufficient.

Question over here?

QUESTION: [Inaudible]

DR. GERBERDING: I think I'm going to ask Dr. Anderson to answer that question for you. Basically, the question has to do with the coronavirus that we're talking about with SARS, what is the degree of homology with the known human coronaviruses? Larry, can you take this question, please.

Again, congratulations for the work that your team has done. It's really terrific.

DR. ANDERSON: Thanks. I think it's a lot of people at CDC. And also help from investigators throughout the world. Part of the WHO collaborating center, and a lot of coronavirologists helped in terms of strategizing. In terms of the question, how related is this virus to the known human strains, OC43 and 229E, what, in coronavirus there has been established three groups that they call 'antigenic groups.' This virus is like a totally separate group, related to part of the coronavirus family, but distinct from all the other known coronavirus -- both animal and the two human strains.

DR. GERBERDING: Thank you.

Let's take a telephone question, please.
MODERATOR: Laura Biel with Dallas Morning News, your line is open.

QUESTION: What is currently known about human metapneumovirus co-infection and whether that may make the disease more severe or more transmissible?

DR. GERBERDING: We are looking for the metapneumovirus here and the other collaborating laboratories are continuing to search for evidence of this virus and other viral agents that could be contributing in individual patients to what we're seeing as a variable clinical picture. Most laboratories are not finding very many patients with metapneumovirus. And so if it's important, its link is not nearly as consistent as the link with SARS. But we haven't ruled it out, and we will continue to look.

I'll take another phone question, please.

MODERATOR: Robin Eisner with msnbc.com. Your line is open.

QUESTION: Yes, Dr. Gerberding, thank you for doing this.

How many other places throughout the world will be doing sequencing of the coronavirus? And is there an estimation as to when that will all be done? And then, if it's not related to any animals or human viruses, how will the sequence data help you find our where this came from?

DR. GERBERDING: Well, in the short run, I don't think the sequence data is going to tell us where it came from. We've got some more work to do. And one of the major steps is we need to go back to the very first cases of SARS that probably occurred in the Guangdong Province, and really do the kind of shoe-leather epidemiology that it takes to know: Who were those people? Where were they? What were they doing? What life were they leading? What did they come in contact with?

And then, for example, if those patients were in a situation where they were exposed to animals, or birds, or some other kind of environment, to go and try to recover viruses from the animal kingdom that are implicated in that detective story.

That's a lot of work, and we are just beginning to take those steps in conjunction with the WHO and the partners in China. And so as have more information there, we will work very hard on identifying the biological linkages.

But it's a story that's going to unfold over some time, and we're just not really in a position to guess right now where that's going to lead us.

Let me take a question over here.

QUESTION: In addition to the work that you just described, what other immediate practical uses are there going to be for the sequence data?

DR. GERBERDING: The most immediate use is likely to be in enhancing diagnostic testing. Because once we have detailed information about the comprehensive genome of the virus, we can make tests that are based on the PCR, where you take a piece of the virus and you can amplify it in the test tube, and it makes it easier to detect in patient tissues.

And we already are doing that test, based on one part of the virus RNA. But if we know the whole sequence, we can create combinations of tests or more elaborate tests that are built on the same principle. And I think getting a rapid diagnostic test is the realistic goal, and we'll be working very hard with other collaborators and with industry on doing just that.

I'll take a telephone question, please.
MODERATOR: Steve Mitchell with United Press International. Your line is open.

QUESTION: The World Health Organization is reporting that this diagnostic PRC test the CDC is employing is, I think they're saying several hundred times more sensitive than some of the other PRC tests, and the CBC might role it out at the end of this week. Can you comment on that?

DR. GERBERDING: Well, we are doing a PPR test and that is a test that's very sensitive; it looks for very tiny pieces of the virus in very low concentrations. And so, it can be extremely sensitive. But we are not going to have a licensed diagnostic test this week. I can assure you of that. The process of getting a test licensed is a step-wise process, just like getting a drug licensed is a step-wise process.

What we're doing now is preparing the reagents and optimizing the method, so that we can get these tests out to the state laboratories are epidemiologic tools.

In addition the FDA is working side by side with us to get the tests into an investigational protocol, so that we can use it for making patient care decisions. And in order to use a test to make a decision for a patient, it is subject to a bit more scrutiny and more evaluation than just something that we put out as an epidemiologic tool.

So that's happening very fast and certainly within a very short period of time--and I can't tell you exactly when--we'll have that formal protocol, so that doctors can use this test to diagnose patients in the actual medical setting.

Finally, getting the fully licensed tests done will take probably several weeks to a few months. And that's just a matter of validating accuracy and performance of the tests under a variety of laboratory conditions.

I'll take a phone question, please.

MODERATOR: Maggie Fox with Reuters. Your line is open.

QUESTION: Well, good timing on that one. Along those lines, a German company said today that they had developed a rapid PCR test and had released it to some centers. Can you comment on that?

And also can you comment on some suggestions I've had that perhaps a test that's been used on some people in China, who were contacts of SARS patients, who have not developed symptoms yet, and they got a positive back?

DR. GERBERDING: Well let me first say that I think the more we get experience with testing, and the more people who are developing tests and deploying them, the better. So I'm delighted if the Germans have a good test. That's wonderful, and we really look forward to learning more about it, and continuing our collaboration in that regard.

There are a lot of tests that are going to be coming out using this technology. It's a kind of standard recipe for diagnosing infectious disease these days, and there are little subtle variations from one test to another. But I think we'll be able to get an optimized test or tests fairly quickly.

With respect to: Do people have the coronavirus in the absence of illness? This is a very, very important epidemiologic question for us. If people are colonized, or carry the coronavirus, and they don't know it, then we wouldn't necessarily have a reason to isolate them. As it turns out, the pattern of transmission that we are observing does not suggest that those people are very important in the spread, because we can link back the chains of transmission to people with symptomatic SARS.

But as we have access to better testing, we may learn more about exactly when people become infectious, and this is certainly one of the questions that we'll be looking into.

Let me take a phone question, please.

MODERATOR: Kathleen Doheny with LA Times. Please go ahead.

QUESTION: Yes. Can you update [Inaudible] preventive measures for travelers going to or returning from affected areas? And I ask this because at least one travel product company that I know of is suggesting antibacterial wipes and a personal air purifier worn around the neck can help. So can you separate the help from the hype for us, for travelers?

DR. GERBERDING: Separating the help from the hype is a very difficult challenge in the absence of all of the data that we would like to have. So, I would rely on the old fashioned approach, which is basically common sense.

This is a disease that is spread primarily by face-to-face contact with infected SARS patients. We don't have any evidence that wearing any kind of commercial and sometimes air purifier adds anything at all to the safety of the traveler from SARS, or from any other infectious disease.

And on the other hand, hand hygiene, whether it's soap and water, or an alcohol-based hand rub, or some combination of the two, is common sense, and should be done as a matter of general personal hygiene, regardless of whether we're in a SARS era or not.

So my advice is to kind of follow the same rules that your mother taught you in kindergarten. Keep your hands clean, and cover your mouth with a tissue if you're coughing and sneezing. And use common sense.

I think we can take one more phone question.

MODERATOR: Mary Harris, ABC news. Your line is open.

QUESTION: Yes.

Dr. Gerberding, I'm wondering if you can comment about the specificity of the tests you developed, and also when will we know the final name of the virus?

DR. GERBERDING: The specificity of the various test that we're using at CDC is still under active investigation, both the PCR-based test as well as the antibody-based test. That's part of the reason why it takes time to get them validated and licensed -- because we must know the sensitivity and the specificity. The only way to know that is to test lots of people with the disease and lots of people without the disease. And that's just a matter of taking some time.

In terms of the naming of the virus, remember we have still not fulfilled the criterion for being absolutely certain that the coronavirus is the cause of SARS. But we're very close, and continue to make progress in that regard. When it is time to name this new coronavirus, it will be decided by an international committee who has global responsibility for naming new pathogens.

So we'll put in our vote, but so will lots of other investigators. And we'll let you know when we learn what they decide.

So thank you very much for helping us with this, and as I say all the time, when we know more, we'll tell you.

Thanks.

MODERATOR: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

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