Published on Mar 01, 2021

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, Chief Medical Officer at WebMD and you're watching Coronavirus in Context. Have you heard about these variants-- the New York variant, the California variant, Brazil variant, South African variant, the UK variant. We've been talking about variants for a long time. But what impact does that have, then, on our behavior and the news? Are we covering them too much? So to help provide some insights I've asked my good friend, Dr. Eric Topol from Scripps. Dr. Topol, thanks for joining again.

ERIC TOPOL: Oh, it's always great to be with you, John.

JOHN WHYTE: Now, you coined this word "scariant," where even with little data about a new variant we have it on major news channels. Are we covering it too much? Or other people will say, you know what? We need to be transparent and get the information out there and let the public decide.

ERIC TOPOL: Well, I think it's really a tricky, John, because, you know, everybody has kind of grown up with the term mutation. And that means there's some change in a letter of a gene code. But here we're talking about 20 mutations, 10 in the business spike protein part of the virus. So it begets this term variant and it only gets upgraded to the term strain when it has true meaningful, important differences.

So we only really have one strain right now, which is this UK variant. The others mostly are in the scariant category whereby we have some concerns. Most of them are innocent. In fact, the most important thing to leave you with today, John, is all variants are innocent until proven guilty. And, so often it's reported, like the California variant was reported as the devil is here, but there isn't any proof that it's guilty. So how can you say the devil is here when there's no proof? So if we assume the best, which we should for variants, then what we want to only take as a high bar threshold when you prove that these series of mutations leads to something that is meaningful, worrisome properties.

And there are three properties, right? One is that it can be more infectious. The second is it can be more virulent. That is, cause more deaths, more hospitalizations, more severe cases. And the third one is that it could have this immune evasion feature, whereby even if you've had COVID you could get it again because your immune system doesn't recognize it. It evades it. Or, if you get a vaccine, it might not work as well against this because it's different than what the vaccines were built on.

So those are the three properties. And so far we really don't have one variant or strain that has all three, which is good. That would be the monster, right? We have one that's the most troublesome, which is that UK variant because it has both the issue of transmission infectiousness, by 50% or so more, and then it also appears to be more with fatal and severe illness. So that's the one we have to be worried about because in the US it's seeded everywhere. And in a couple of states, namely ours here in California and in Florida, it's up around 20%. When it gets to 40%, that's when you start to see the trouble. So we are in this kind of phase where we're lulled into that everything is good and the cases are coming down and we could see a big turnaround in a few weeks.

JOHN WHYTE: But how do we really know how widespread these variants are? Where there are some estimates that less than 1% of samples-- some people are saying it's 0.5%-- are tested. And then we have to extrapolate it to a broader population. Are we really that good at math and determining how widespread these variants are if we're doing such little testing? And I should point out, individual patients can't request this variant testing and can't even get the information back as to whether or not they had the variant. So how realistic is it when we say how widespread it is in the public media?

ERIC TOPOL: Well, what's happened is, ever since this whole issue of the variants arose-- and you remember up and through the calendar year of 2020, it really wasn't a problem in the US. It was at the very end in December and since then where we started to have this awareness. So genome surveillance is going into high gear. So in San Diego, for example, we're now sequencing 20% of the samples. So not 1%. Not what it was 0.3% countrywide.

And so things are going into high gear for sequencing because you mentioned an important point. If you have a vaccine and you are a rare person who fails-- namely you get COVID after your two doses and a couple more weeks and you're at full immune response-- we need to sequence that because we need to know what is the root cause for that. And also I don't think we have to sequence all. No country is sequencing all except perhaps very small countries like New Zealand or Australia are a high proportion. Even the UK is only sequencing about 6%, 7%. So we're going to get up to that level.

In the meantime, we know what we're dealing with and we know that the screening-- before you actually sequence there's a thing called S drop which is a assay that's run. And we can tell what's going on now around the country. And that's why we know Florida and California are the troublespots.

JOHN WHYTE: The rate of new cases seems to be plateauing in some areas and people automatically ascribe that to the variance. Do we know that?

ERIC TOPOL: Well, we had, in recent weeks, this tremendous dissent. Really kind of unprecedented even though we had of course recovered from the monster surge. And then the question is, why? Because we don't have enough people vaccinated to explain that. We don't really have enough people with natural infection immunity to fully explain that. Is it behavior? Are we more geared up because of the scariants and the real variants? You know, what is it? We don't really know. But what we are worried about now is that we have one trend coming down, which is great, and then we may be starting to see the other one going up. And in between where we are right now you could miss it because it could be flat.

And so only in the next two or three weeks will we know where we're headed. If we dodge this, if we don't get the beast of B117, it'd be phenomenal because then we'd kind of have a clear path to an exit ramp. And so this is what's in our way. Because the other immune evaders, like the South African that you mentioned and the Brazil, and possibly New York, which is looking troublesome, those, what do they do? Well, they don't transmit so much. Their main issue is that they could cause re-infections or the vaccine resistance. That's a tiny problem relative to hyper transmission and lethality increase. So we can deal with those better and they may slow a little bit our exit, but they won't be anything like this B117.

JOHN WHYTE: Does the presence of these variants make you rethink whether we should delay the second dose to get more people vaccinated?

ERIC TOPOL: Yes. You know, I had been against the second dose change because I like to stick to the protocol and you have all these great trials with 95% efficacy. But right now there's three alternative dosing schedules that could get more people to start with their vaccine immune response. That doesn't mean we wouldn't give a second dose, but it means that they may get it at six weeks or eight weeks instead of at four or three weeks. So I'm in favor of that now, as well as the half dose Moderna where there is a randomized trial that looks very good. As well as not giving two doses to people with prior COVID because one dose looks quite good.

So if we use those conserving strategies just for the month while we're waiting for-- we have a supply issue right now and we have a B117 potential onslaught issue right now. So if we just use these strategies to get us through a replenishment and re-supply of vaccines, we might be able to help fend off this one major obstacle that's holding us back.

JOHN WHYTE: Because variants won't survive if there's no host for them to infect. So the more people we get vaccinated is a good thing and we need to have some speed with that. Last thing I want to ask you is about preprint. And really about pre-preprint. And recently you expressed frustration, maybe even some anger, over that people are commenting now actually on drafts of manuscripts that haven't even been submitted for preprint. Where is this going? And is there a push to be-- some people will argue-- to be provocative on the news because that's going to get you more interest? But aren't we so to talk about science and listen to the scientists and then we're putting out draft documents that haven't been subjected to any type of review.

ERIC TOPOL: Yeah. Well, let's talk about preprinting. Great question. But before I get to that, I just want to emphasize one thing. A lot of states now are going into major relaxation modes. Getting rid of their mitigation, whether it's your restaurants and gatherings and whatnot. And that's the wrong thing to do right now because we may be facing our biggest challenge yet. All you have to do is ask people in the UK, Ireland, , Portugal Israel. I mean, they had the worst of the whole pandemic. And remember, countries, like some of them, really had control of things all the way through. This can be a real beast, but we'll see. But don't relax now. This is the time to keep getting containment so we're ready.

Now, the preprint thing, I was really stirred by this. Because on Monday when the "LA Times" came out with the "devil is here" and they talked about a preprint which hadn't been published-- and here it is Friday, it's still not published-- I can't review that data. Well, I can because the journalist sent it to me. And in fact, like every different newspaper had this preprint except for the "Preprint Server." OK? And so--

JOHN WHYTE: It's a pre-preprint. That's why I'm saying that.

ERIC TOPOL: Yeah. It's a pre-preprint. The whole idea with preprint is, if it's really important you post it so that the whole biomedical community can look at it and can make their own assessment. Is this real and how good is the evidence? So this one hasn't even been posted. And meanwhile, it became New York Times, Washington Post, Sacramento Bee, and LA Times. It was on every news channel about the California variant and this-- I really got upset because, you know what? If the investigators believed it's so important, why is this preprint not posted?

Now, then later in the week there was another twist of this, which was very different. So one of the best science journalists at the New York Times, Apoorva Mandavilli, she published a preprint from Caltech about the New York variant. And she also had gotten a copy of the Columbia Medicine paper that was going to be posted the following morning, which essentially replicated the Caltech, and that variant is concerning. The proof is still not there. But it looks like it's an immunity evader, not a B117 beast hyper transmissible virus.

Anyway, it was reported responsibly, it raised concerns, but there, again, when it was published, that preprint wasn't available to look. Only one of those, the Caltech one, was. So without getting too, you know-- that one was small compared to the California variant. That one, I think, qualifies as capital S scariant because we still don't have anything to look at. And that means it's not the journalist's problem in my view, John. It's the researchers. If they're sending preprints to the journalists and making claims, then why aren't they posted?

We already have embraced preprints during the pandemic in a major way. But the issue here is that it only takes a day or two to get something posted and then everybody can look at it. If you're going to talk to the journalists, it's worse than a press release because now you're really trying to inject all this science in there and you're showing data. It's not like a press release. And it's getting published in newspapers that we rely on for facts. And we can't check it out.

So I'm asking that whenever the journalists publish about preprints that at least we know it's posted or it's imminently posted for sure, that you could check with the bio-archives or MIT archives or whatever. Because we need to weigh in on that. We need to help others interpret for the public and for the medical community, is this the real deal or is this a scariant?

JOHN WHYTE: In the meantime, we need to be aware, but to your point, not scared. And when we have questions we can turn to Dr. Eric Topol's Twitter page. So I encourage everyone to follow you on Twitter. I want to thank you, Eric, for always providing us the facts, the insights, that we need to stay informed and to be safe as well. So thanks for all you're doing.

ERIC TOPOL: Oh, hey. John, thanks to you. You're leading the way and I'm glad to join you today.