Eric Topol, MD, Discusses the Omicron Variant, Therapeutics, and Rising Case Counts

John Whyte, MD; Eric Topol, MD


December 03, 2021

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JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, the chief medical officer at WebMD.

How concerned do you need to be about the Omicron variant? Is it more transmissible? Are the vaccines going to hold up against it? Joining me today to answer those questions is Dr. Eric Topol.

Eric, thanks for taking time today.

ERIC TOPOL: Always good to be with you, John.

JOHN WHYTE: I want to start off with, as you know, the Omicron variant. What do listeners need to know today? Everyone wants to know: Do we know -- is it more transmissible?

Do we know if the vaccines will hold up against it? And if we don't know now, why are people saying, “Well, we'll know more in a couple of weeks”? What's going to happen? Give us that timeline and your best guidance.

ERIC TOPOL: Well, first, John, I don't think there's real cause for a lot of anxiety because this strain, if it turns out -- I think it will likely be called a strain, or variant, as it now -- has lots of mutations. But we've already seen other variants with lots of mutations, maybe not as much as this one, that don't have much functional impact. So using that as a background, this one will likely have some evasion of our immune response so that people who've already had COVID or people who've been vaccinated, even perhaps with a booster third shot, there may be some vulnerability. But most likely, it's not going to be a serious matter. That is, most likely, especially with a recent third shot, within recent months of that, the ability to override Omicron is likely.

So there's a lot of craziness out there because of what's happened in the one province in South Africa, and indeed, there's a major outbreak there. But remember, that's not against Delta. They basically had contained everything there, so it's basically a virus variant that's really in a proliferative mode there. With a lot of cases, not a lot of difference in the hospitalization pattern, any worse or better than prior waves in South Africa. We've seen cases, obviously, in over 20-some countries, but there's no other outbreaks, at this point.

JOHN WHYTE: Then why do people seem very concerned about this? You can't turn on the news without some dire warning from a scientist pontificating about it.

ERIC TOPOL: Well, I think the first thing was that when the sequence -- which was brilliantly and rapidly reported by the South African scientists -- when you look at it, you say, oh, my gosh, this is really ugly. There's 30 mutations in the spike protein, 15 in the receptor binding domain. I mean, this looks like it could be really horrendous, but then you look at what's happening around the world.

And as I said, there's an isolated major outbreak. And we've yet to see major transmission chains develop elsewhere. It doesn't mean we won't, but we don't want to get ahead of ourselves. The physician in South Africa who made the first -- saw the first patients -- actually wrote an op-ed saying this is an overreaction.

And so I think these are some important points. But John, to get to your other question: Why will we know more in 2 weeks, or even, really, in 1 week, now? And that's the lab studies because we can take serum from the people who've been vaccinated and test it against the virus and see how well it neutralizes Omicron. My guess is it will be reduced, but it won't be below the levels that our vaccines have effectiveness. Maybe there'll be some marginal reduction of vaccine effectiveness, but hopefully, they'll hold up reasonably well.

JOHN WHYTE: Well, like many, I follow your Twitter feed, and I wanted to bring up this issue of genomic sequencing. You mentioned it. But you also pointed out, in a graphic, how low our percentage is of actually doing testing.

So can you talk us through that? Because in many ways, how do we know that it's not here or more widespread? We do such little genetic sequencing. Why is that?

ERIC TOPOL: Well, interestingly, John, our sequencing of the virus has really picked up in the last couple of months, gotten up to 10% of the cases. So when we were having 80,000 cases, that would mean they were getting 8,000 sequences a day. But the problem is, as you alluded to, we're not doing enough testing. We're at one-fourth or one-fifth the testing of the U.K. and Israel, respectively.

Now, beyond that, it's also which viruses you're sequencing, from which patients or people. So the problem we have is that every breakthrough that winds up in the hospital or infection, or every hospitalization, for that matter, or people coming in from airports with infections -- the key samples are not necessarily getting sequenced. So we have multiple issues about lack of detection that we know.

JOHN WHYTE: How do they decide what to sequence? I mean, there seems to be no order to this, and you're right. We're at 10%, which, let's be honest, is not really that high. It's much better than we were 18 months ago, as you point out, when we were in single digits. But how is that a robust surveillance system?

ERIC TOPOL: Not at all. We were, cumulatively, for the pandemic, 3½%. And there are some countries, obviously, smaller than ours, that are 100% sequenced.

JOHN WHYTE: When we talk about the percentage of people in the US that are fully vaccinated, it's around 60%. We're not even in the top 25 countries, in terms of percent of their citizens vaccinated. So we're focusing more on therapeutics, and recently, the FDA granted emergency use authorization to Merck's drug, molnupiravir. But the vote of the advisory committee was pretty close, around 13 to 10.


JOHN WHYTE: So I want to ask you your thoughts on it and why that vote was really pretty close.

ERIC TOPOL: Yeah, that first announcement that Merck made about their drug made it look awfully good, with a 50% reduction, about a seven per 100 absolute benefit for death and hospitalization. Then when they presented the data at FDA yesterday, and of course, the FDA briefing documents, all of a sudden, that benefit had slipped down to 30%, with less than three per 100 absolute people benefiting. And obviously, there's also this risk because the mechanism by how it works is lethal mutagenesis, that it just mutates the virus until it just is -- it's over and out.

So weighing the benefits, which were relatively small, modest, with the risk that are not fully defined because we have a limited trial sample, I think that it was a tough call to give it an emergency use authorization recommendation. Now, we'll see what the FDA will do. Most likely, they'll ratify that, but it isn't the pill we had hoped.

The next one, that will be soon under review, is the Pfizer pill, Paxlovid. It looks far better. Hopefully, their analysis won't change when they present it, but it had, actually, an 89% reduction, relative seven per 100.

And it doesn't have the problems of mutations. It works much higher upstream in Mpro, the main protease, so I'm looking -- I'm actually pretty excited about that pill. And unfortunately, I was thrilled when Merck made their initial announcement. But ah, they didn't really have, interestingly, John, a good excuse for why the data changed so much. That is, they had an interim analysis and then had the final analysis, and it was just markedly different.

JOHN WHYTE: Now, I'm just going to throw this out there because I feel there's this trend, and I want to get your thoughts on it. So when we've looked at therapeutics early on -- convalescent plasma, remdesivir, now here, early on -- the data always looked encouraging. Convalescent plasma is a whole other story, but let's take it for what it is. And then when we started to have more real-world evidence, effectiveness decreased, in some situations, pretty dramatically, even in this example.


JOHN WHYTE: So the criticism could be we're doing something wrong, we're working too fast. What are your thoughts on this? We're seeing this as a consistent type of response that, as we're doing it in real-world, it's a challenge. Should we be doing these trials differently?

ERIC TOPOL: Well, if you use the vaccine trials as the model, where they're very large --

JOHN WHYTE: Yeah. 40,000 people, multiple trials. Here, we're talking hundreds, maybe a couple thousand.

ERIC TOPOL: The striking part there, of course, as you well know, is that they came out with 95% efficacy, then when the real-world studies were done, they were 95% effectiveness. So they matched up really well. The problem with remdesivir is the first major trial that supported efficacy was small. You know, it was in the thousands, not tens of thousands.

And so you get, sometimes, a skewed or hyperbolic sense of -- and that's, of course, what happened with the Merck pill at the interim analysis. It had a very limited number of people in it. So we need bigger trials. That's something, of course, that has been vital. The U.S. has never really done, except for vaccine trials in the pandemic -- it's really been U.K., Europe that have really done the large trials to help illuminate what are the effective or not effective therapies against COVID.

JOHN WHYTE: Is the FDA being too easy on sponsors right now? Historically, there has been this inherent tension between regulators and sponsors, and many people will say that's the way it should exist. People should be skeptical of the data. Now we're talking much more about collaboration. Have we gone too far? And in terms of using emergency use authorization, become a little more easy grader, so to speak?

ERIC TOPOL: Absolutely. Particularly the last run of the FDA in the last administration when they gave full approval to remdesivir, I mean, and convalescent plasma. And they had to withdraw all these things later. They haven't withdrawn remdesivir, but it really hasn't held up well. So you're right.

The other thing I just would want to mention is there's a real difference between a repurposed drug versus a drug that was designed to tackle this virus. And so that's the difference, interestingly, between the Merck pill and the Pfizer pill. The Merck pill was set up to be tested against influenza and equine encephalitis and things.

Whereas the Pfizer pill was actually derived from SARS, the original SARS, to try to match up against the differences in SARS-CoV-2. So I like drugs that are designed, and treatments, that are not -- it's like repurposing a gift. It's not quite ideal, as compared to --

JOHN WHYTE: No, no, you're not supposed to repurpose gifts. Yeah. But Pfizer's drug is also used as a combination with antiretrovirals that we use in HIV. So it's a little different. Now, what is similar about them is they were both in unvaccinated populations. They both were early on.

And that brings us to your other topic that you've been hot on, is the issue of testing. That we're not doing enough testing. So here, we're saying we're going to use these drugs early on within the first 5 days. Yet, we know we're not doing enough testing, whether it's rapid testing, rapid antigen testing, or PCR testing. So what do we need to be doing to improve testing?

ERIC TOPOL: Right, this has been the abject failure of the United States from day zero, day one of the pandemic. Never got its testing act together. We know we can do PCR testing at scale. We've miserably failed with that. However, we know, from many other countries, that doing rapid home antigen testing works really well. And we have never geared up for that.

That is, countries make that freely available. And each person, if they want to get it, just goes to a local pharmacy or distribution center, picks up a big pack of rapid tests. And that's what we should have here. And they shouldn't have to pay for it and pay a lot for it. And there's limited supply, and we don't have -- the FDA has been a bottleneck for getting more tests. You know, there's 60 cleared by the European medical authorities. There's a limited number, a handful, and only really one that's had a small availability.

So we're not taking this seriously. We have this paternalistic thing -- which lasted for a long time at the FDA -- that oh, it needs to be done centrally. Home tests, people won't be able to do it, the data won't get reported to the local authority. I mean, forget that. We just need to have the tests, and indeed, the rapid tests are more important right now to know whether someone is infectious, not just if they're carrying some viral remnants around.

JOHN WHYTE: So we really want to encourage people to get those rapid tests.

I want to end with some misinformation out there that's really about understanding data. And it's a question that we often get at WebMD that I want to pose to you. So people are looking at Europe and high vaccination rates. Many of them have had mitigation efforts, yet then we see breakouts. We see large numbers of cases. And especially those that are unvaccinated are saying, “Hey, see, I told you. The vaccines don't work.”

Help them understand why that doesn't mean that the vaccines don't work. How do we put that into context for them? Countries that have higher vaccination rates than we do, more instances of lockdown, yet still have increased frequency of cases and a fair number of hospitalizations.

ERIC TOPOL: Right. Well there's two kind of categories there, John. If you look at the ones in Western Europe where they have quite high vaccination rates -- places like Spain and Portugal, Denmark -- you see in those countries, yeah, there's some increase in cases, but there's hardly any increase in hospitalizations and deaths.

Now the increase in cases. Who are those masked men and women? Well, they're not masked, for one, OK? But more importantly, they're unvaccinated, largely. So even if you have 75% of your population, total population, vaccinated, it's that 25% that are the most attributable to the spread.

Now also, there's the waning. So if people are out more than 6 months, haven't gotten a third shot, they're also -- although less so -- they're part of the transmission chain. So in those countries, we have this one category as lots of cases, yes, those are those issues, and relatively small in the way of serious illness, hospitalization.

Now in Eastern and Central Europe, it's a different story. Their vaccination rates are quite low, some many, well lower than the U.S., which is ranked below 50th in the world right now. And they're having the same problem we had in our Delta surge. Very high hospitalizations, not uncoupled with the cases, so they both track together.

So the difference is when you have a good immunity wall, you won't have nearly as much hospitalizations and deaths. We don't have a good immunity wall. Austria has more of their people vaccinated than us, and even with the lockdown, they're having serious problems. So 59% isn't going to cut it.

And also, John, remember: Every day we have more people waning, significantly more, than we have new people getting vaccinated. So we're going in the wrong direction, rather than getting up to 80%, 85%, where we need to be.

JOHN WHYTE: And you've been out there saying now's not the time to take our foot off the gas, that we've got to power through this.

But I want to end with asking you: How do we know when the pandemic ends? What metrics do we --

ERIC TOPOL: Yeah, well, it's that transition to the endemic state, which is when there's a low level of cases. We almost know --

JOHN WHYTE: What's low? Is it 10,000? Is it 1,000? Is it, what is it?

ERIC TOPOL: Well, you can make up a number. You could say it's less than 10,000. But if they're all in one neighborhood, that's not good.

JOHN WHYTE: That's true. That's an epidemic, yeah.

ERIC TOPOL: We're a really big country, and if we're having very tiny outbreaks, and it's under control, it's contained, whether that number is 3,000 a day or 20,000 a day -- it's not, I can tell you, it's not 90,000, like it is right now and on the way up.

JOHN WHYTE: We have 50,000.

ERIC TOPOL: So, you know, ideally, it's less than 10,000 total a day, distributed relatively evenly. So it's kind of in check. That's what an endemic state looks like. That's what Japan is like right now. They're in an endemic state. And frankly, there are other countries around the world that have done such a great job with vaccination. They're going to be there very quickly.

JOHN WHYTE: All right.

Well, Dr. Topol, I want to thank you for taking time today, helping to educate us about whether or not we need to be concerned about Omicron. Is it a “scariant”? We talked about that before.

ERIC TOPOL: It has to be determined. If a few weeks from now, we have bolstered our confidence level, then we'll reclassify it as a “scariant.” Right now, though, it looks like it's troubling. It's troubling, but nothing to get too hyped up about.

JOHN WHYTE: We're going to check in with you then. Thanks for taking the time again.

ERIC TOPOL: Thank you.

JOHN WHYTE: Good seeing you.

This interview originally appeared on WebMD on December 03, 2021

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