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Eric J. Topol, MD: Hello. This is Eric Topol, with Medicine and the Machine at Medscape. I'm really delighted to have Dr Tom Frieden join me today. We have so much to talk about, so welcome.
Thomas R. Frieden, MD, MPH: It's great to speak with you, Eric. I'm looking forward to the conversation.
Topol: We've seen a lot of Dr Frieden on TV and in the media because he was the CDC director throughout the Obama administration. His distinguished background is really quite extraordinary. He was at Oberlin College and then Vanderbilt, Columbia, and Yale, where he earned his MD and MPH and had infectious diseases training. Then he kind of took over New York City, first as part of the public health system, and then as commissioner of the New York City Health Department. That was a stepping stone to the CDC, where he was director for 8 years. Now he's on to a major campaign in cardiovascular disease with Resolve to Save Lives. We'll talk about that. So, Tom, you've been preparing for this pandemic throughout your career, right?
Frieden: All of us in public health anticipated that there might be a pandemic like this, but we kind of thought it would be influenza. Although over the past decade or two, it's been clear that it's a mistake to try to predict what the next pandemic is going to be. We didn't think SARS would hit us, or MERS, or that H1N1 would come from Central America or that Ebola would spread in an area of Africa that it had never been in before. And what that tells us is one essential thing: that we need a pluripotent public health system. We need to be ready for any threat. And that means rapid detection and rapid response.
Ebola vs COVID-19
Topol: You oversaw the Ebola response, which was in many ways a model that averted what could have been a real disaster here in the United States. Can you give us your sense about what was different about Ebola? Obviously, it wasn't as transmissible, but it was highly deadly. How did it go so well with Ebola, with the CDC, in the United States?
Frieden: There were plenty of ups and downs with Ebola. The fundamental difference, to be frank, is that Ebola isn't nearly as infectious. It only spreads through close contact, during burials, in hospitals or in families, or rarely through sexual contact.
The critical moment in Ebola happened not in the United States or Guinea, or Liberia, or Sierra Leone, but actually in Lagos, Nigeria. This was in July of 2014 when a person from Liberia who was very sick went to Lagos and died. That person had been told he had Ebola, but he didn't tell anyone else. And then an outbreak started in Lagos. Just to give you an idea, there are 10 times more daily flights in and out of Lagos than there are from Guinea, Liberia, and Sierra Leone combined. And way more overland traffic as well. So if that outbreak had gotten out of control in Lagos, I believe it would have spread throughout Nigeria and much of Africa — not just for months, but for years.
For a few days, the response was not good. It was disorganized. And then the polio eradication infrastructure snapped into place to address Ebola in Lagos. When one patient went to Port Harcourt and started another outbreak in another city of Nigeria, that infrastructure was amazingly effective at stopping those outbreaks in just a few generations of spread with limited loss of life. That was the pivotal moment. If that hadn't happened, Ebola might have been spreading for years in Africa.
Topol: I didn't realize that. That's striking. While we're on Africa, it's been a positive outlier in the pandemic. Still today, there's very little sign of a COVID problem in Africa. Except for what we saw in South Africa with the B.1.351 variant, Africa has held up really well. Why do you think that is? Is it because of public health or underreporting? Or is it yet to come? What's your sense about Africa?
Frieden: There are a few different things going on. I will say that my organization, Resolve to Save Lives, works with more than 20 countries in Africa and has for the past 4 years on issues of epidemic preparedness. First and foremost, a lot of these countries are much more familiar with epidemic control than the United States is. When we talked about contact tracing in the US, people said, "What is that?" When we talk about it in Africa, they say, "We got that." Almost immediately there were thousands of contacts under daily monitoring, really without much effort. They've done that for other diseases.
But there are a number of things going on. One, Africa was very proactive with closures. In fact, we spearheaded a group called PERC—the Partnership for Evidence-based Response to COVID-19 in Africa, which did surveys in 20 cities of 20 countries. We found that those closures were very painful socially, economically, politically, and health-wise. This was a situation where the cure was actually worse than the disease. So the countries modulated and reopened. One factor was a very robust public health response with rapid testing, border controls and border testing, and good contact tracing. There is a lot going on that we need to give African public health and medical leaders credit for.
Second, it's a much younger population. And as you know, the gradient between young and old in the lethality of this virus is just enormous. There are countries in Africa where less than 4% of the population is over the age of 60-65. That compares with 20%-plus in parts of Europe. So, essentially it's a much less lethal virus, not because the virus is any different, but because the population is different.
Third, there are some data that there was a substantial underdiagnosis of death from COVID in Africa. A very important study done in Zambia from autopsies found that only about 1 in 10 patients was diagnosed with COVID-19 before death. So the number of deaths may have been higher than recognized, though not as high as they might have been because of the public health measures and the age of the population. And perhaps it's not there yet. What we're seeing around the world is that there's a certain amount of randomness in how explosive the spread is. A few superspreader events can create a vicious cycle that ratchets transmission up in a huge way, which is most likely what's happening in Michigan today.
CDC Fumbles, and What Else Went Wrong
Topol: You are bringing up a very important issue about the places that become hotspots and those that don't. I want to get back to that. But before we do, we've been communicating throughout the pandemic. One of my greatest frustrations was that the venerable world-model CDC that you directed, and I've seen throughout my career, took some hits. I would send you direct messages saying, "Things would be so different if you were running the CDC." I really believe that. It was a very tough time for the CDC. Weren't you frustrated about this?
Frieden: It was a very tough time. They made a big mistake with the lab test early on, although really by the third week in February, that mistake was fixed and the lab test was working well. But that was a critical blind spot early in our response. But you have to look at testing more broadly. The FDA should have allowed private labs and academic labs to begin testing much sooner than they did and to do it much more easily. The Health and Human Services Department should have pulled together all the private testing companies — the Quests and Labcorps of the world — and gotten them very proactively testing, which is what happened in South Korea. So it wasn't just a CDC fumble there, but it certainly was a mistake. It contrasted with what happened when H1N1 hit, and we developed a very accurate PCR test within days and got it approved and sent out to more than 100 countries. We had millions of copies right away.
It was stunning to see that kind of a problem. If you look objectively, how much of a difference that would have made isn't so clear. But it was clearly a black eye, something that shouldn't have happened. We still don't know exactly why it happened. There should be an external investigation — not to blame anyone, but to make sure it doesn't happen again.
More broadly, the issue was that to respond effectively to an epidemic, you need three things: organization, science, and communication. What we didn't have through all of 2020 was organization, science, and communication. It was never clear who was in charge, who was doing what; there was no organization, no plan even. We were talking about bizarre possible treatments rather than saying, look, we're learning about this every day. And as we learn, we're going to tell you more. A lot of us, myself included, didn't think that masks were going to be very important back in January and February of 2020. As the data came out, it became clear that they're very important. That wasn't because we were wrong. That's how science works. You learn and you adjust your recommendations.
Similarly, we're learning today about the J&J vaccine and the possibility of blood clots.
Then you need communication. CDC literally wrote the book on how to communicate in a health emergency. Be first, be right, be credible, be empathetic, and give people practical, concrete, proven things to do. If you think of those five principles, you couldn't possibly have violated them more than the prior administration did. They weren't first. They weren't right. They weren't credible. They weren't empathetic. They didn't give people practical things to do. So of all of the failures of the prior administration, I think you could point to communication as being one of the main ones. In terms of CDC specifically, they weren't allowed to speak directly to the American public, and they were doing a lot of great work but nobody could hear about it. They were stopping outbreaks in nursing homes. They were doing important epidemiologic studies, but they weren't allowed to talk about it. That was a major challenge. And, of course, for the hard-working doctors and scientists and others at CDC, it was, I'm sure, demoralizing to be doing important work and then not to be able to make sure that work was being optimally used to protect people's health.
Topol: It is amazing to think back about all the breaches that happened, like the censorship of the MMWR and the fact that the director didn't stand up to the administration when the whole organization was subjugated. It was an extraordinary time and hopefully one we will never see again. You would never have tolerated that under your leadership.
COVID Vaccines: Speed, Safety, and Luck
Topol: Now, vaccines. You've obviously been involved with lots of vaccines over your career. And this one seemed like pulling a rabbit out of a hat. We had an existential threat to the species here, and then within a matter of only 10 months, we go from the identification of the pathogen sequence to big trials. Can you put that in perspective? There are actually people who think that it happened too fast, that there's something wrong with the vaccine. Can you help us on that one?
Frieden: It is a stunning success story of science. And Eric, I've seen your pinned timeline on Twitter about this, and it is one of the remarkable stories in all of history. But one thing that's really important to emphasize — and this is something that health professionals can explain to patients — is that the COVID vaccines were not rushed in the sense that we cut corners on safety. They didn't spring magically out in a year. We're talking about decades of research on mRNA and vectors, and then buckets of money being put into this, saying, "Money is no object. We're going to bet on multiple horses and see which succeeds," and that has clearly been very important.
And then we got lucky in a few ways. Mother Nature does a pretty good job here. Our own immune system is pretty good after having COVID, maybe 94% protection against serious illness for at least 8 months. That's impressive. With a disease like malaria or TB or HIV, Mother Nature doesn't do very well against these pathogens, and we still don't have vaccines. But if the body can mount a good defense, we have a much better chance of doing it with the vaccine.
So we got lucky with the technology and with our immune system. But I don't think anyone thought that we would have 90%-95% or close to 100% protection against severe COVID disease. I haven't heard of anyone who has been fully vaccinated and has died from COVID, and more than 100 million people have been vaccinated in the United States. So this is a remarkably effective vaccine. And the mRNA technology is a game changer. It may be able to be used for other vaccines, for biologicals, and for other things. It's a really exciting technology coming out of this pandemic.
But the data on safety are very important for people to understand. The clinical trials for these vaccines were larger than usual. More than 100,000 patients participated. There were no serious adverse events. When millions or tens or hundreds of millions of people are vaccinated, you may see rare, serious adverse events. But it went so fast because we cut red tape, not because we cut corners on safety.
Topol: You mentioned a lot there that deserves emphasis. Number one, that the natural infections engender such strong immunity, which may go on for years — at least 8 months. And that is different from these other pathogens: influenza, HIV, or TB. That's important. It's directed to the spike protein, which is interesting as a primary clone of antibodies. But the vaccine is even better than the natural infection because you get even stronger titers and broader antibody-neutralizing activity. We're lucky.
How Concerned Should We Be About CVST?
Topol: Now, J&J has had six cases, all women, all young (between 18 and 48) with this cerebral venous sinus thrombosis, also known as CVST. Only one of these cases occurred during the J&J vaccine clinical trial. It was a 21-year-old man, and they stopped the trial in October very briefly to review that case. So now we have seven cases out of about 7 million J&J vaccines that have been administered — 1 in a million. It might be more than 1 in a million because it's possible that not every case of CVST has been fully documented.
I want to get a further perspective. You do a clinical trial in 100,000 people and then administer more than 800 million doses of the vaccine in 154 countries, in hundreds of millions of people. We know that there will be some things that we don't anticipate, right?
Frieden: Absolutely. I am concerned, though, because a very serious adverse event, even if it's only one in a million, is something that needs to be looked at carefully. And even before this, I was a fan of the mRNA vaccines. They're easier to tweak in case there are variants. They're less susceptible to production delays. We've seen production problems with both the AstraZeneca and J&J vaccines. It's a biological process. You're growing something. In contrast, the mRNA is basically a chemical process, so it's much more predictable. In terms of ramping up global manufacturing, the time to start is much faster with the mRNA vaccines; you can start in as soon as 6-9 months. Right now, we are not on track to vaccinate the world until 2023, so there's a real need to increase manufacturing capacity. I think of the mRNA vaccine as an insurance policy against variants, against production failure, and now maybe against rare and serious side effects.
But you have to put it in perspective. One in a million vaccinees may develop a serious adverse event vs about 1 in 200 people with COVID infection dying from it. That's a very large order-of-magnitude difference, especially in places where COVID is spreading a lot. There is always going to be a risk-benefit ratio and we need to learn more. Maybe we can identify risk factors that predispose people to an adverse event, whether it's medicines they are taking or other factors. Maybe we can identify ways to detect and treat this condition early with immunoglobulins or other treatments that could improve the outcomes and get the serious adverse event rate down to 1 in 10 million.
As I've been saying for many months, this is the most complicated vaccination program in US history, and it's going to be the most complicated in global history as well.
Topol: This is really important because you're touching on the mRNA vaccine. There hasn't been a case of CVST yet with the mRNA vaccine, which is really interesting. There have been some cases of the platelet count dropping, but none of this most dreaded type of exceedingly rare blood clot. That's surprising; maybe we'll see it. But so far, the mRNA vaccines seem to be exempt from this.
A COVID Surge: Mitigate or Vaccinate?
Topol: You've mentioned the situation in Michigan. I want to get your readout on the current state of the pandemic, because a lot of people were thinking it was over. And then we started seeing the B.1.1.7 variant coming into the country. Michigan is turning out to be the bellwether, with cases rising and hospitalizations spiking. We're now seeing neighboring states like Minnesota and Illinois starting to show the same trend. What are your thoughts about where we're headed now?
Frieden: Stepping back, I feel like we don't always learn. When COVID first hit Italy, the thought was, "It's not going to come here." And when the B.1.1.7 variant hit the United Kingdom, again, it was like, "It's not going to come here." I understand that people are really tired; there's pandemic fatigue. But we've learned a lot. We've learned that schools can be open safely with precautions. We've learned that outdoors is generally fine. So there's a lot we can do, but certain things remain really risky. Church choirs, bars, and restaurants are things that I wish we would wait a little longer for because we will have strong vaccine-induced population immunity plus natural immunity within the next couple of months. But we don't have it yet.
We have this confluence of circumstances where we've now vaccinated so many seniors (and almost universally in nursing homes) so that we have a drastically lower risk of death from COVID. The hospitals are now seeing people in their 40s and 50s because most people in their 60s and 70s have been vaccinated. The vaccine effect is major. We have to factor that into our decisions and discussions about closures, but not about masking. There's no economic harm to masking. The only freedom a mask inhibits is the freedom of the virus to spread and kill people. So I don't have any sympathy with the idea of freedom from masks. You don't have a right to walk into a grocery store and infect someone with a virus that's going to kill them when you could just wear a mask and prevent that from happening. But I do think we need to balance reopening with safety. And we have to understand that for the places where cases are exploding today, vaccination is not going to tamp it down. Masks and closures are going to tamp it down. It takes 2-6 weeks after vaccination to have an effect.
Aiming Our Shots Better
Frieden: There is a bigger issue with vaccines that transcends the situation in Michigan or the upper Midwest, and that is aiming our shots better. We're not doing a great job of aiming our shots. We've done well with seniors generally. But as an epidemiologist, I look at the micro level, at communities, and I see that the places with the highest vaccination rates have the lowest disease rates — not because they are preventing disease with vaccines, but because they are rich folks. In contrast, the places with the highest case rates have the lowest vaccine rates because they have poor, disenfranchised populations that are not well served. "First come, first served" is a terrible formula for equity.
This isn't just bad for the ethical reason that it's morally unacceptable. It's bad for epidemiologic reasons. If you vaccinate someone in a high-risk community in a high-risk group, you may well stop transmission and save lives. If you vaccinate a healthy middle-aged person who's teleworking, you're probably not going to prevent any cases or any deaths. Not every vaccination has the same value. We have to do better at aiming our shots where they'll do the most good.
Topol: That can't be emphasized enough. The people who come to the vaccination sites are the ones who are cautious. Those who can't make an appointment or don't show up are the people who need it most.
In recent days, some leading experts like yourself have said that in Michigan, we should rely on mitigation — closing things that have been opened too quickly. But I also think we could learn from Israel and the UK experience. Israel is fully open, and loading up on vaccines aggressively helped them get reopened. Here, we have severe fatigue and people just want to open. With Michigan as a precedent, we should do both mitigation and vaccination: getting shots to the right people, as many first shots as we can. We need to be more aggressive with vaccination — not a 9-to-5 thing, but getting vaccines into doctors' offices and mobile units and any other way we can get shots administered. I hope that when we have these challenges, we won't just rely on mitigation. We've already seen that that doesn't work in some places. We can do both of these things. We didn't have vaccines during the first few waves here. We have them now. Yesterday, Rochelle Walensky at the CDC, who I have great respect for, basically said we should just go ahead with mitigation. I don't know about that.
Frieden: I think we can do both. One of the big challenges for the federal government is what do they do in terms of perverse incentives? If you move vaccine from places that are doing well to places that are doing poorly, then a month from now when the places that were doing well get hit, they will say, "We wouldn't be getting hit if you left us with our vaccine." So the government has a legitimate challenge in terms of equity with vaccine administration.
I think the way out of this is to reverse what Julian Tudor Hart wrote decades ago in The Lancet, on the inverse care law. Hart wrote that the availability of good medical care tends to vary inversely with the need for it in the population served. And we are really seeing that across the United States — not in all communities, but in many. If we can aim our shots better, and make sure, for example, that if you live in a zip code that has a COVID rate above X, you can walk in for a vaccine; you don't need an appointment. And we're going to set up 18-hour shifts, 6 days a week. And if the community sent out their workers and organizations and community leaders to say, "Come on, get vaccinated," then you're aiming your shots better. I did a simple calculation that a well-aimed shot can save 10 times as many lives and prevent 100 times as many cases as a poorly aimed shot. And this isn't necessarily about moving vaccine between states but about how we're focusing them within communities. It's great to be focusing on giving 2-4 million vaccinations a day. That does an enormous amount of good building up our population immunity. But we also have to think of how we are aiming those shots.
It's All About the Great Outdoors
Topol: The point that you're highlighting is critical, and it has been missed along the way using numbers alone. The challenge is getting vaccinations where they are most needed. We haven't cracked that throughout the country, if you look at who is getting the vaccines.
Compared with Michigan, what about Florida or Texas — places that have been wide open, abandoning the idea of mitigation totally? We don't see outbreaks there. Does this go back to your earlier point regarding superspreader events that just happen? Are there any other explanations for this discrepancy?
Frieden: We really don't know for sure. One thing is that there's a lot more outdoor activity in the South than in the North. It's warmer there. Being outdoors is hugely important. Ventilation is important and outdoors is the best ventilation imaginable, so much so that it is one variable that may be driving it. It may be bad luck with superspreader events. You've seen some documentation of single clusters spreading all over the country, so it may be a question of time. I hope Florida continues to do well, but it's possible that they will start getting hit hard in a few weeks. We just don't know. This is one of the unanswered questions of this pandemic. And there are others. We have a lot to learn still.
Topol: Apropos to that, we saw some countries in Europe that didn't have nearly as big a problem with the same variant that we're dealing with right now, the UK B.1.1.7.
Frieden: If you look at India, it's very puzzling. They had a lockdown that didn't go so well, but they did crush the curve. There was very little COVID and then it came roaring back. So why did it go away? Why did it come back? Sometimes these are stochastic events; they occur, and it may be a matter of being in the wrong place at the wrong time, or if you're the virus, the right place at the right time.
Topol: We have a very opportunistic enemy for sure. And mysterious in some regards, such that we still don't understand many aspects of how it operates, even 15-18 months later.
One thing I wanted to call out is your ability to communicate. You mentioned that as one of the three pillars of the CDC and you're still doing it, even though you're not the CDC director. Every Friday you would put out a Twitter thread (@DrTomFrieden) often as many as 20 connected posts. This had to take hours. It's a great public service, one that you weren't required to do. You just did it. I could just see you toiling away on a Friday evening, putting all this together. Can you tell us about that?
Frieden: It started in January of 2020. Six important articles had come out that week. I'm not running the CDC anymore, so I had time to read them very carefully. And I thought, it's Friday night. I'll have a single glass of wine and write a summary of these six articles. I got so much feedback, including from people in the government, who said, "We don't have time to read them carefully. Thank you for that." And then as it became less possible for CDC to say what was happening, I thought, well, if I were at CDC, this is what I would be emphasizing for this week. And then it became an issue of it being so hard to keep up. The developments in science and epidemiology and control were so rapid that in the course of any one week, there was a lot of epidemiologic news. Some of the commentary by very well-meaning people didn't really get it right from a disease control perspective — understanding what's really important, what can make a difference, and what's a flashy headline vs really big news. So it became a pattern. I've recently tried to stop doing it, but each week, new things keep happening.
Topol: I noticed that your post said it was your last one, and then you did another one the following week. I can't give you enough kudos for that.
Resolve to Save Lives
Topol: After you were the CDC director for 8 years in an Obama administration, it must have been hard to find the next arc of your career, but you did it. Can you tell us about what you're doing now since you started Resolve to Save Lives?
Frieden: I was very fortunate. I knew that I would leave after 8 years. The last person to last 8 years at CDC was Dave Spencer, and he was appointed in 1966. Eight years is enough, regardless of what happened with the election in 2016. I was able to think about the big picture. What are the areas that are truly on the bubble, where a nongovernmental organization, correctly positioned and generously funded, could make a huge difference?
I identified two broad areas. One is epidemic readiness. We realized after Ebola that the world was far too vulnerable. A lot of progress was made identifying what needed to be done, but there was not a lot of progress getting it done. So one of our areas was closing the epidemic preparedness gaps.
The second was cardiovascular health, something near and dear to you as well. As you know, cardiovascular disease is the world's number-one killer. Within cardiovascular disease we identified three things: the global elimination of trans fat, a reduction in sodium consumption, and the control of hypertension. Those three things, done correctly, could prevent 100 million deaths over a 30-year period. With funding from generous donors — the Chan Zuckerberg Initiative, the Bill and Melinda Gates Foundation, Bloomberg Philanthropies, and more recently the Start Small Foundation — we've been able to ramp up activities in both areas that have really exceeded our very ambitious goals.
In the epidemic-preparedness space, we're working in dozens of countries and we're seeing substantial progress with countries able to find and stop outbreaks in hours to days where it used to take weeks to months. These countries have tracking systems, surveillance systems, and laboratory networks that they didn't have before — resources in the tens of billions of dollars being spent on strengthening preparedness that weren't there before. And with COVID, the potential to really make the world drastically safer from future pandemic threats.
In terms of the cardiovascular work, we have seen a domino effect with the world becoming free of artificial trans fat. India just took action to become trans fat free with best practice options. Trans fat elimination alone will save more than 17 million lives over 25 years, and we're seeing it expand. Hypertension treatment — it turns out you can really do hypertension treatment. Globally, we control maybe 10%-15% of the blood pressure among people with hypertension. Yet the medications don't have to cost more than $10 annually, and protocol-driven care can be done very effectively at high rates. This comes from experience with tuberculosis and HIV. We know that protocol-driven care does really well for the vast number of people. For complicated patients, you can do something else. But these are winnable battles. These are areas where we can make a huge difference.
So, I feel very fortunate that we have this opportunity and some initial funding to do this. We're now entering into our second 5-year period and thinking of what to do next in these and other areas. It's been a lot of fun and a great privilege. And it's great to work with so many terrific people around the world on something that can make such a difference in so many people's lives.
Topol: Well, let me just say, we're the ones who are fortunate, Tom. Many people might have thought you would have made your peak impact as CDC director and stamping out major outbreaks around the world. What you are doing is extraordinary, so congratulations on that. We'll be following Resolve to Save Lives and your own resolve to make the world a healthier place for people. Thanks so much for joining us today.
Frieden: Well, thank you, Eric, and thanks for what you do. You've been a model on Twitter, in communications, and your work with Medscape and others. So it's really a great pleasure to speak with you.
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Cite this: Tom Frieden on COVID: CDC Fumbles, Blood Clots, and New Approaches - Medscape - Apr 15, 2021.