From the JAMA Network, this is JAMA Author Interviews. Conversations with authors exploring the latest clinical research, reviews, and opinion featured in JAMA.
Dr. Howard Bauchner: Hello and welcome to this author interview. This is Howard Bauchner, Editor in Chief of JAMA. As many of you know, who've listened to these podcasts before, I've been fortunate to interview Dr. Tony Fauci, Director of the National Institute of Allergy and Infectious Diseases. And today I'm interviewing Zunyou Wu, who is the Chief Epidemiologist at the China Centers for Disease Control. Welcome Zunyou.
Dr. Zunyou Wu: Thank you.
HB: Thank you so much for joining me. I think our listeners are really quite anxious to hear from you but before we start, firstly on behalf of JAMA, the United States and I think most of the world, I hope you and your colleagues in China are doing well. I know it's been an extraordinarily difficult time the last few months. And I'm quite sure you're working virtually every day very long hours. So, I wish you and your colleagues the best. Could you tell our listeners, Zunyou, where you trained and what you currently do?
ZW: My name is Zunyou Wu from China CDC. I was trained in the University of California at Los Angeles with a PhD degree in 1995. After coming back to China, I primarily work on HIV/AIDS. Also, when the emerging infectious diseases coming, I also join the fight for this epidemic. For example, in 2003 I joined the entire epidemic for SARS. For this coronavirus, I joined in the middle of January. So, my role is to try to collect data, the individual cases, and to try to use epidemiology analysis to look at the pattern and the trend of the epidemic. Try to interpret the result. And give guidance what's mostly important to address the issue.
HB: Well, I think the United States and other countries have a great deal to learn from what's been going on in China. So, I'll ask a number of questions. But before we get to the questions, Zunyou, can you tell me as of today, which is February 13th, and for me it's 8:30 in the morning. For you it's 10:30 or 11 p.m. at night, February 13. What are the number of cases that are currently now been reported in China? And the number of deaths? The number of cases outside of China is actually quite small. But what are the number of cases in China?
ZW: So, we collect data every day by midnight. So, we download data from our National Reporting System, we do an analysis and send a report to the National Health Commission. So, now I have data available in my hand as of February 10, 2020. So, that was two days ago. So, by February 10 we have totally reported 42,638 confirmed cases, reported 1016 deaths. And also, we have 21,675 suspected cases.
HB: As you know, because I know you participated in a number of discussions, some interesting discussion has occurred about the definition that the CDC in China is using. So, you just indicated there's about 43,000 cases, but then you also just indicated that there's approximately 21,000 other designations. What is the 21,000?
ZW: It's suspected cases. So, that means they have not been diagnosed as confirmed cases yet.
HB: And are those individuals who have symptoms, and don't have diagnostic testing, or are those individuals who've had diagnostic testing but have not developed any symptoms? Or, is it both?
ZW: Most of these suspected cases is they do have the clinical symptoms, but do not have the laboratory test yet. Because the capacity to provide the timely laboratory test, it's insufficient particularly in Hubei, Wuhan. So, we try to support capacity in the Hubei province. So, central government send many health workers, including laboratory technicians to Hubei and Wuhan, try to address that issue.
HB: The capacity to do massive or a large number of diagnostic testing is just limited... as it would be in any country.
HB: You're a trained epidemiologist, you've done remarkable work. Can you tell me what your sense is of the epidemic in China over the last week or two weeks? Do have a sense of what you think is occurring?
ZW: So, if we look at the epidemic, we have 2 important indicators. So, for each individual case they did have two dates. One is onset of symptoms. One is the date of reporting. So, the public only knows how many people been reported. And also, the government announced the number of people being reported. So for each individual, we have the epidemiological investigation try to understand what's the onset of the illness. So, we use that data to reconstruct here the epidemic curve. Based on that, so the epidemic occurred peaked in January 23 to 26th. But for most people in the general public, you cannot see that. Only way to analyze the data can present that way. So, the epidemic, now it's actually going down. That is because we have the very strict control measures. Because we also have the Spring Festival people stayed home that isolated or reduced the people movement. After that long holiday, people coming to work. So, the future direction of epidemic is still uncertain yet. So, we prepare possible upcoming epidemic.
HB: But it sounds like your sense from looking at data on a daily basis, and the investigations that you've been able to do, is that actually the epidemic is improving not getting worse. I want to make sure I understand what you just said.
ZW: That's correct. So, they have two broad part of epidemic. One is in Hubei and Wuhan City. That epidemic is different from the rest of the country. So outside of Hubei is mainly originated from Hubei, then they do have secondary transmission, mostly at cluster, at a family, does not spread it to the community. So, the epidemic going down both based on the onset of illness and also based on the reporting of date. However, in Hubei and Wuhan, the epidemic is still very complicated yet because the number of people infected are huge. So, the medical treatment and diagnoses and capacity cannot absorb. So, in the recent days you can see larger number of reported cases continue to increase. Also, not stable. So, that makes the interpretation very difficult for people outside.
HB: Do you have a sense, you know if you just look at the numbers, you know it's 43,000 or so, and 1000 deaths, that gives you a case fatality rate of 2 to 3%. But some people have projected that it's actually much lower. Because there's likely many other people who are infected who haven't either come for medical attention or aren't yet defined as having been infected. Do you have a sense of what you think the case fatality rate actually is?
ZW: Right now, the case fatality it's as you just said about 2%. It was over-estimated, because we do have asymptomatic cases. Also, if we compare the mortality in Hubei, Wuhan and outside of Hubei, Wuhan, so, in other provinces, the mortality it's about 1%.
HB: Right, and if I'm not mistaken in Hubei there's about 32,000 cases and there's about 10,000 cases in the rest of China. Is that accurate? I think those are the numbers I looked up this morning.
ZW: You know Hubei accounts for about 70% of the total cases in China.
HB: So 70% of the 42,000 is about 30,000. So, there'd be about 10,000 cases outside. And you said the case fatality rate outside of that area's lower.
HB: Now, there's been some discussion about asymptomatic communication of the disease. And defining an asymptomatic state is quite complicated. Part of it is in the case series that JAMA published, many people had unusual symptoms; diarrhea, for example, or GI upset. Which isn't usually associated with respiratory pathogens. So, I think defining an asymptomatic state is not easy. What's your sense about asymptomatic communication of the disease or spread of the disease? Do you think it's real or it's still uncertain?
ZW: I think our understanding about the spectrum for coronavirus will still continue to increase. So in the early stage, we do not believe that there were asymptomatic cases. However, with more people being tested, and we do observe a certain number of people being tested, PCR positive, but with no, any symptoms. So, the most common symptoms we observe is fever, dry cough, and fatigue. Also, some have diarrhea. So, for asymptomatic cases, they have none of these symptoms at all. However, which you already know is really they are virus carrier, or it's in the early stage, they may with time moving, they will develop symptomatic cases, or diagnosed cases. So, we still need to observe the asymptomatic cases for certain period of time. So the study is ongoing.
HB: Now, the other issue that's come up and we're about to publish a research letter in the next day or so. Today's Thursday, I think we're publishing it tomorrow about a case series in infants. Children under the age of 1. There had been initial reports that it seemed as though infants and children were being spared. But I don't think that's the case, do you? In the data that you get can you look at the age spectrum of those people? The 42-odd-thousand? Can you see disease in infants and young children?
ZW: Yeah, we do. We have very, very small number. In the early stage because of the exposure it's in the food market. For the food market, it's many adults there. So, if we look at its distribution, the majority are younger adults. So, let me look at this data. For people ages 30 to 79, they're accounting for 90%, 90% of total cases. The children, a limited number because their exposure, the opportunity to be exposed is small. So mainly after the virus spread after, outside Hubei, then the more cases for children were reported.
HB: Now, is there anything emerging yet on treatment? Most of the case series when we published that have been in other journals have been really symptomatic for those, particular those older adults with comorbid conditions, who were quite ill. It's mostly been symptomatic, people have tried some antiviral, some antimicrobial agents, corticosteroids have been reported to be used. Some HIV drugs. Is anything emerging around treatment, or is it too early, or too uncertain to really be definitive about treatment, other than supportive care?
ZW: Right now, it's more supportive care. And doctors try every effort that they could. For example, one medicine treat HIV called Kaletra and they used and the patient themselves feel good. So, one doctor he suffered with the coronavirus. Because he's a doctor and he knows the Kaletra can be effective for the MERS then he took the medicine, then he shared his experience. Right now in China we do have the clinical trial to test the one of medicine still not in the market yet. It's developed by Gilead. It's remdesivir. It's a new medicine has not been marketed yet. But is very effective on in vitro.
HB: And that's being tested in a clinical trial?
ZW: Yeah, in a clinical trial. And Gilead provided 800 doses for the clinical trial. The trial already ongoing for about a week now.
HB: And is it for individuals who are quite ill in the intensive care unit? Or is it general population? Who's eligible to be in the trial?
ZW: It's in hospitalized.
HB: Hospitalized patients.
HB: And is there a control group or a placebo group?
ZW: I'm not directly involved. My understanding is that [inaudible] the trial. So, it follows the requirement for the trial. I think they have control. I'm not sure if they have the placebo. But they do have a comparison group.
HB: Now, you're a clinical epidemiologist. You have an enormous amount of experience looking at epidemics and now pandemics. What have been the surprises for you about this?
ZW: It's very hard to predict fully because in the early stage, we saw that it's a very severe new epidemic. And if we look at severity, the mortality is not as high as SARS. However, it's very contagious. So from Hubei spreading to the rest of China only takes about a few weeks. So, the spreading of virus very quickly. To have an understanding of this coronavirus is still, it's another, to answer the question, need to scientifically study to answer that.
HB: Yeah, some people have suggested it's behaving more like certain strains of flu that have occurred in the past rather than coronavirus with SARS or MERS. It's been interesting. There's been a bit of discussion about that.
ZW: I think that if you look at the transmission part, it looks like flu. However, the clinical symptoms are totally different. Some of the cases look like soon to be recovered. However, just in one day or two days people die. The pathogenic of the virus is still a mystery.
HB: Now, obviously there's a great deal of interest about how coronavirus moved through different populations from animals to human beings. Is there any additional information that's emerged about what the origins of this particular coronavirus may have been?
ZW: We do not have answer yet. Virologists are trying to find the answer. The epidemic originates from one of seafood wholesale market. So, some wild animal sold at the market. We do not know exactly which animal, or which origin it come from.
HB: Now, obviously the vast majority of cases have been in China. Far less around the world, and that's despite a remarkable amount of travel between China and the rest of the world, when it is likely that that people were infected. So, I've been impressed with what the public health communities and infectious disease individuals have done in countries around the world including the United States. Because it really has not spread substantially outside the US, except obviously for that ship in Japan. What do you think you would want to say to your other epidemiologists and clinicians around the world about how they should think about the infection? What advice would you give us?
ZW: I think if we look at the past few weeks, China's government took firm action quickly limiting people move in/out of Wuhan. That slow down and reduce the epidemic and reduce the transmission from Hubei to the rest of the country. And also, it has reduced the spreading from China to the rest of the world. However, there are still some cases reported from neighboring countries. So, the epidemic, it's without border. So, early detection is very important. So, the surveillance program, the very sensitive surveillance to detect the additional cases, and also immediately have the isolation control methods. It's very important that you reduce the scale of the epidemic.
HB: Obviously a great deal of information crosses my desk as well as I read extensively about this every morning, and throughout the day. And I think you're well aware there's been concerns raised about whether quarantines are effective or not effective. And I'll let other people weigh in on that, ultimately, with respect to this epidemic and pandemic. But it's certainly an interesting question. And I know your government has been really quite aggressive about trying to really constrain the virus to a limited number of areas. Can you tell me what it's like, I mean the numbers that we hear in the United States and around the world are remarkable that China has constrained the travel of over 50 million people. That is a remarkable number. How has China been able to do that?
ZW: I think because of epidemic and alert to the public. And also, we do have lessons learned in 2003 from SARS outbreak. And we understand isolation quarantine is the most effective measure to control this epidemic. If we look at the epidemic outside of Hubei, so as long as we take these measurements, and the epidemic is mainly contained at family, or clustered in the family. So, we look at all the cases outside of Hubei provinces. So, cluster cases, family cluster cases account for 83%. That means people are, because of Spring Festival, they go return to home from Hubei. They brought the virus to home they only transmit it within home. Not beyond the home, not into the community. So, that means, identify close contact, and quarantine or isolate them is a good strategy to prevent the epidemic from a family cluster to the community.
HB: Two questions have come in over social media. And I'll read them to you, or I'll paraphrase them. First you mentioned the clinical trial that's ongoing. Have you had much contact with the different groups that have been trying to develop a vaccine? And do you have any information about vaccine development? Dr. Fauci had mentioned that he thought in the best of all worlds, we could get a vaccine into phase 1 trials in three to six months. Other people have said closer to a year. Do you have a sense about vaccines?
ZW: I do not know exactly how long it take. To my knowledge, a few groups of scientists are doing vaccine research. So, optimistically you may take about at least a few more months. So, China in I think 2009 when the flu coming, it only took about six months to have the vaccine ready for vaccination. So optimistically it may take about at least half a year to get a vaccine ready.
HB: Right, well, I'm guardedly optimistic that the epidemic and pandemic will be really much quieter in the next few months. And that ultimately, we may decide we don't need the vaccine. Diagnosis in immunocompromised individuals is difficult because they may not respond to the PCR. Do you have a sense of diagnosis in individuals who are immunocompromised? I assume it would start with what symptoms they have, and do they have a good story for exposure to someone who was diagnosed. But do you have any advice about diagnosis in individuals who are immunocompromised?
ZW: We do not have the understanding about this issue yet, because epidemic just start a few weeks. So, the studies are still ongoing, and we do not fully understand. So, immunologist and virologist may the study in this area.
HB: Another question that's come up in social media. I'll read it to you and it's again about the numbers that we talked about earlier. That you had mentioned about 40, 42,000 cases, 70% are in Hubei. And then another 21,000 where there's uncertainty. But that the comment was an almost 50% increase in cases as of yesterday or today in Hubei province reports 14,840 new cases. Is this simply catching up? And they put that in quotes, is this catching up, as more testing is done? Can you comment on that?
ZW: That number also surprise me as well because previously we have accumulation of cases waiting for diagnosis. And because for capacity to provide timely laboratory confirmed cases is very difficult. Then the clinician suggests [the diagnosis], because in Hubei, they just use clinical diagnoses for cases.
HB: And do you have enough diagnostic tests now? The CDC just sent quite a few out. And unfortunately, there was a report that came across my desk very quickly that they had to recall some for different reasons. But does China have enough diagnostic tests to make diagnoses?
ZW: We do have sufficient diagnostic tests; however, it is requires the laboratory capacity and also need trained technician to perform the test.
HB: And I think the world watched with amazement as China constructed two hospitals in the period of two weeks. I think most of the world just watched with amazement. It was remarkable. Is it your sense now that there's sufficient clinical facilities to care for individuals who need to be hospitalized or are seriously ill? Or is China still struggling with this new number of individuals who are so ill?
ZW: So, China try their best to make treatment available for people who suffer with coronavirus and 2 new hospital built just less than 10 days. And also, the local has mobilized hotels and other facilities as temporary healthcare setting, provide treatment for patients. Right now, the condition is going to improve.
HB: This is Howard Bauchner, Editor in Chief of JAMA. And I've had a remarkable guest this morning. Zunyou Wu, who is the Chief Epidemiologist for China CDC. He's an adjunct professor of epidemiology at UCLA and the director of the Division of HIV Prevention at the China CDC, or obviously as you can tell from this conversation for the last three months, he's certainly been working on the coronavirus epidemic and pandemic. Zunyou, I can't thank you enough for joining me today. I know it's really quite late. I'm sure you've been working incredibly long hours. So I do want to thank you. And I really can't emphasize enough that on behalf of JAMA, the United States, I assume the world that we wish you and your colleagues well in caring for these individuals. I have been impressed with what I've seen and read about the capacity for China to respond to this epidemic. So again, thank you so much for joining me today. And please stay healthy.
ZW: Thank you, it's my pleasure.