Variants or 'Scariants': Are the Threats Real or Just Media Hype?

John Whyte, MD, MPH; Eric J. Topol, MD


March 02, 2021

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  • "Scariants" are COVID-19 variants of concern but without proven or peer-reviewed data. "All variants are innocent until proven guilty."

  • Of the highest concern are variants that are infectious, virulent, and have immune evasion. We don't have any variants with all three of those properties. However, the UK variant is more infectious and more virulent.

  • While we wait for new vaccine supplies, we should consider alternative vaccination plans: Get more people vaccinated, including delaying the second dose to 6-8 weeks after the first; giving a single dose to people with prior COVID-19 infection; and giving a half-dose of the Moderna vaccine.

  • Many states are relaxing mitigation strategies, which is the wrong approach right now because "we may be facing our biggest challenge yet" with the UK variant.

  • Researchers are making claims and sending pre-preprints — which are not even on a preprint server yet — to journalists but not to the biomedical community.

This transcript has been edited for clarity.

John Whyte, MD, MPH: 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, the Brazil variant, the South African variant, and the UK variant? We've been talking about variants for a long time, but what impact does that have on our behavior and the news? Are we covering them too much?

To help provide some insights, I've asked my good friend Dr Eric Topol, from Scripps, to join me. Dr Topol, thanks for joining again.

Eric J. Topol, MD: It's always great to be with you, John.

Whyte: 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? Other people will say, "You know what? We need to be transparent and get the information out there and let the public decide."

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

We only 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 is that all variants are innocent until proven guilty. 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? If we assume the best — which we should for variants — then what we want is a high-bar threshold, when it's been proved that these series of mutations lead to something with meaningful, worrisome properties.

There are three properties. One is that it can be more infectious. Second, it can be more virulent (ie, cause more deaths, hospitalizations, and more severe cases). Third, 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 from what the vaccines were built on.

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 (the UK variant) because it has both the issue of transmission infectiousness (by 50% or more) and it also appears to have more fatal and severe illness. That's the one we have to be worried about, because in the United States it's seeded everywhere. In a couple of states — namely California and 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 phase where we're lulled into thinking everything is good and the cases are coming down, and we could see a big turnaround in a few weeks.

Whyte: But how do we really know how widespread these variants are? There are some estimates that less than 1% of samples are tested — some people are saying it's 0.5% — 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? I should also point out that individual patients can't request this variant testing and can't even get the information back as to whether they had the variant. How realistic is it when we say how widespread it is in the public media?

Topol: 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 when we started to have this awareness.

Genome surveillance is going into high gear. In San Diego, for example, we're now sequencing 20% of the samples. Not 1%. Not what it was, 0.3% countrywide. Things are going into high gear for sequencing, and you mentioned an important point. If you have a vaccine and you are a rare person who fails — namely, you get COVID after two doses and after a couple more weeks you're at full immune response — we need to sequence that because we need to know what is the root cause for that. 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. Even the UK is only sequencing about 6%-7%. 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 an assay that's run — can tell what's going on now around the country. That's why we know that Florida and California are the trouble spots.

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

Topol: In recent weeks, we had this tremendous dissent. It was really kind of unprecedented, even though we had recovered from the monster surge. Then the question is, why? Because we don't have enough people vaccinated or 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? What is it?

We don't really know. What we are worried about now is that we have one trend coming down, which is great, and 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.

We will only know in the next 2 or 3 weeks where we are headed. If we dodge this — if we don't get the beast of B.1.1.7 — it would be phenomenal because then we'd have a clear path to an exit ramp. This is what's in our way, because the other immune evaders, like the South African, Brazilian, and possibly the New York variants, which are looking troublesome, what do they do? Well, they don't transmit so much. Their main issue is that they could cause reinfections or vaccine resistance. That's a tiny problem relative to hypertransmission and lethality increase. So, we can deal with those better, and they may slow our exit a little bit, but they won't be anything like this B.1.1.7.

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

Topol: Yes. 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. Right now there are 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 6 or 8 weeks instead of at 3 or 4 weeks.

I'm in favor of that now, as well as the half-dose Moderna (where there is a randomized trial that looks very good) and not giving two doses to people with prior COVID, because one dose looks quite good. If we use those conserving strategies just for the month while we're waiting for vaccines — we have a supply issue and we have a B.1.1.7 potential onslaught issue right now — if we just use these strategies to get us through a replenishment and resupply of vaccines, we might be able to help fend off this one major obstacle that's holding us back.

Whyte: 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.

The last thing I want to ask you is about preprint — and really about pre-preprint. Recently, you expressed frustration, maybe even some anger, over people commenting on drafts of manuscripts that haven't even been submitted for preprint. Where is this going? Some people will argue that there is a push to be provocative on the news because that's going to get more interest? Aren't we supposed to talk about science and listen to the scientists? We are putting out draft documents that haven't been subjected to any type of review.

Topol: 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 restaurants and gatherings and whatnot. 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, and Israel. They had the worst of the whole pandemic. Remember, some countries really had control of things all the way through. This can be a real beast, but we'll see. Don't relax now. This is the time to keep getting containment so that we're ready.

Now the preprint thing. I was really stirred by this because [on February 23] the LA Times came out with "The devil is already here," and they talked about a preprint that hadn't been published. By that Friday, it still was not published and I couldn't review that data. Well, now I can because the journalist sent it to me. In fact, every different newspaper had this preprint except for the preprint server.

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

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 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 news in The New York Times, The Washington Post, The Sacramento Bee, and LA Times. The California variant was on every news channel and I really got upset because, you know what? If the investigators believe that it's so important, why is this preprint not posted?

Then later in the week, there was another twist of this, which was very different. One of the best science journalists at The New York Times, Apoorva Mandavilli, published a preprint from Caltech about the New York variant. 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 one, and that variant is concerning. The proof is still not there, but it looks like it's an immunity evader, not a B.1.1.7 beast hypertransmissible virus.

Anyway, it was reported responsibly and it raised concerns. But again, when it was published, that preprint wasn't available to look at. Only one of those, the Caltech one, was. 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. It's not the journalists' problem, in my view; 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 of this science in there and you're showing data. It's not like a press release. 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, at least we should know it's posted or it's imminently posted, so you could check with bioRxiv or the medRxiv or whatever, because we need to weigh in on that. We need to help others interpret for the public and for the medical community whether this is the real deal or a "scariant."

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. I encourage everyone to follow you on Twitter.

I want to thank you, Eric, for always providing us with the facts, the insights, that we need to stay informed and to be safe as well. Thanks for all you're doing.

Topol: John, thanks to you. You're leading the way, and I'm glad I joined you today.

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