Ep. 58: Variants of Concern Explainer with Dr. Aisha Khatib

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The coronavirus has mutated into numerous different substrains, including the three so-called “variants of concern”: B.1.1.7 from the U.K, B.1.351, first identified in South Africa, and P.1, first found in Brazil. In this episode, Medcan’s chief medical officer, Dr. Peter Nord (above right) interviews the clinical director of travel medicine, Dr. Aisha Khatib (above left) about how the VoCs are different from the original coronavirus. Are they more or less deadly? How infectious are they? Do the variants make a third wave inevitable? And: How do the vaccines protect against the variants? Our experts translate all of it for general listeners in easy-to-understand terms.

Insights

According to Dr. Aisha Khatib, analysis shows that variant B.1.1.7 is more transmissable than previous strains. “The big concern that we saw was how quickly it became dominant and circulating in Europe,” says Dr. Khatib. “Within two months, it became the dominant strain. Now, that's fast, that’s very fast.” Previous variants spread much more slowly. In fact, B.1.1.7 is showing signs that it’s up to 50% more transmissable than the original coronavirus strain. (Time code 6:30)

The vaccine may not protect as well against the variants of concern, Dr. Khatib says. Early indications suggest the vaccines may not be as effective against B 1.351 and P.1. However, Dr. Khatib cautions that this is a difference only in degree. The vaccine still offers protection against the variants — it’s just, it' may not offer quite so much protection as it might to the original strain. “Even if that effectiveness drops down to 70%, that's still going to provide protection in the community,” she says. (Time code 8:45)

Don’t be too concerned if the vaccine doesn’t currently protect against the variants of concern, says Dr. Peter Nord. Vaccine manufacturers believe that it’s comparatively easy to tinker with the vaccine to retool it to provide widespread protection specifically against the variants. Dr. Nord says one vaccine manufacturer told him they could do it within six weeks. So at some point in future we all may have to get booster shots on top of our original vaccine jabs. “I think there definitely will be boosters that are required,” says Dr. Khatib. “I know Pfizer and Moderna are looking at one… And the nice thing is… it's actually relatively easy to tinker with the vaccine to accommodate for these variants if needed to create these booster shots. So that's kind of a reassuring thing as well.” (Time code 22:00)

Links 

  • Find Dr. Aisha Khatib on Twitter @aishakhatib

  • The World Health Organization did a “Science in 5” feature on variants that explains things well. Check it out

  • The Globe and Mail: ‘We now have two pandemics’: Variant COVID-19 cases soar in Ontario. Story.

  • U.S. Centers for Disease Control and Prevention resource on the variants of concern.

  • The Economist describes the evolutionary mechanics affecting SARS-CoV-2, with the implication that natural selection doesn’t seem to influence its lethality.

  • Are you an employer seeking expert guidance to manage COVID-19 risk? Medcan’s Medical Advisory Services can help. Email corporatesales@medcan.com to learn more.

The Variants of Concern Explainer with Dr. Aisha Khatib final web transcript

Christopher Shulgan: This is episode 58 of Eat Move Think, and I'm Christopher Shulgan, the show's executive producer. This episode is about coronavirus variants. What's officially known as SARS-CoV-2 has spawned dozens of different variants, with three in particular generating concern: B117 from the UK, B1351 first identified in South Africa and P1, first found in Brazil.

Christopher Shulgan: The fact that coronavirus has variants is not unusual. This is how natural selection happens. When anything multiplies, mistakes creep into the replication of genetic material. Mutation is the result. Coronavirus variants were inevitable.

Christopher Shulgan: There is something unusual about the evolution of SARS-CoV-2. Most of the time, virus mutations result in variants that are less lethal than the original variety. For viruses, natural selection tends to favour mutations that are best able to spread to more people. That fact spurs an evolutionary drift toward variants that have less severe and longer infection periods.

Christopher Shulgan: That dynamic doesn't apply to the coronavirus, however, because it's most infectious just as people first show symptoms. How deadly the virus is has virtually no effect on how well it spreads. Consequently, the mutation process and natural selection are free to yield more deadly variants.

Christopher Shulgan: Which brings us back to B117, B1351 and P1. Are they actually more deadly? More infectious? Do they foretell a third wave, or can vaccine distribution stamp them out before they become as threatening as some fear them to be?

Christopher Shulgan: In this episode, Medcan's chief medical officer, Dr. Peter Nord, talks through the variants with our clinical director of travel medicine, Dr. Aisha Khatib. It all amounts to a compelling explainer designed to answer frequently asked questions in easy to understand terms. Here's that conversation.

Peter Nord: Well hi, Dr. Khatib. Great to have you here on this episode of Eat Move Think. There's been a ton of questions over the last couple of weeks about these variants. A little scary. And so what we thought we would do today is just go through some of those questions and see if we can create a little bit more understanding, you know, separate some of the facts from the fiction as we move forward through this next couple of months, as these variants are coming online pretty strongly. This week, we saw up to 40 percent of the positive cases in Ontario are actually due to variants. So that's a bit of a surprising number. Just to start with, we've seen three new variants of concern—the VOCs as they're known—of the Coronavirus: the B117, the B1351 and the P1. With the viruses constantly mutating, why are these three more concerning than the others? And what are the differences between the three variants?

Aisha Khatib: Great. Thank you Dr. Nord for having me on Eat Move Think today. So yes, let's get right on into it, because there is a lot of discussion about the variants of concern. And the other concern is that potentially heading into a third wave because of these variants. So the first thing to go back and just kind of have an understanding about is, is basically what is a variant, and why are we so concerned?

Aisha Khatib: So we know with viruses, they mutate. That's what they do. It's a natural process that they go through. And specifically with RNA viruses, their one of the viruses that actually have a higher mutation rate compared to other organisms in the animal kingdom if we look at it. However, if you look at other RNA viruses compared to COVID, such as influenza and HIV, the RNA virus for Coronavirus is much less of a mutation rate. So we also know that variants are—what we know is basically we get a mutation in the replication of the virus. So what happens is when a virus infects, it attaches onto a cell, it gets into the cell, and it replicates.

Aisha Khatib: Every time there's a replication, you can actually have a mistake that's made in the genetics of that replication. And when that mistake is made, that is what we call either a mutant or variant. And so up until now, we've seen many, many variants for Coronavirus in particular since the start of a pandemic. And sometimes these mutations are mistakes that are made, can actually have absolutely no impact, right? They can make actually no difference at all. But otherwise, sometimes they can actually be more detrimental and cause a shift or a change in the behavior of the virus. And that's what we're actually seeing with these variants of concern.

Aisha Khatib: What makes these three that you've mentioned, the B117, the B1351. And the P1 so concerning is the fact that the variation in the mutations that we're seeing now for these three are more specific to the receptor binding domain of the virus, or what we call the S gene or the spike gene. And that's why there's so much discussion about it, because it can make an impact in regards to how easily it can infect, the increased number of transmission, and also the discussion about the decreased efficacy of vaccines. Because as we know, there's two reasons that we're concerned about these spikes. One is it's the way that a cell gets infected by the virus. And two, it's a target of our vaccines that have been developed, specifically the Pfizer and Moderna vaccine.

Peter Nord: When we hear the word transmission, some people are thinking, wow, it's actually more easily transmitted from person to person. But it's more about the stickiness almost of the variants into these receptors that you were just talking about. Isn't that right?

Aisha Khatib: Yeah, so when we talk about increased transmission, there's different mechanisms that we talk about. And you can actually have a combination of those that leads to that increased transmissibility. What's more concerning about these variants in particular, so the B117 originated in the United Kingdom back in September, 2020. The big concern with that one is that we saw was how quickly it became dominant and circulating in Europe. Between November to December, within two months, it became the dominant strain. Now, that's fast. That's very fast. If you look at the original variant that came into the US back in May, for example, there was another variant called DG14G. And that variant, that took months to really spread into the US population. So comparatively, we talk about this increased transmission, and particularly for B117, it's showing almost to be up to 50 percent more transmissible than the novel Coronavirus that we were dealing with last year in the beginning of this pandemic.

Peter Nord: That's interesting. And let's say we had our population in Ontario and Canada 100 percent compliant with wearing great masks, two-metre distancing, social distancing, physical distancing, hand hygiene, not touching our face, doing all of the things that we've been asked to do. What would that do to the transmissibility? Or that chance that that new variant is going to take over here?

Aisha Khatib: The reality is if you look at the public health measures that we're using right now, those are really at minimum what needs to be done to really kind of modify, to bring down this transmission. Unfortunately, as we're seeing despite the stay at home orders and despite the lockdown, yes, we have seen numbers go down for the original, the older variants of the virus. But despite that, we're seeing more and more dominance in these variants of concern. And whether or not the measures that we're using currently are enough is really the question. And I think vaccination is really going to be the one key thing that is going to be key to bring down that transmission that we're seeing in the community.

Peter Nord: Well, yeah, and another question that stems from that is the fear that the new variants could be vaccine resistant. What's the risk of that, and are future vaccines out there that can deal with that?

Aisha Khatib: Yeah, so that's actually really interesting. And there's a lot of discussion about that. And I know there's a lot that's been in the news in regards to especially the B1351, which was the variant that originated in South Africa, and the P1 variant that originated in Brazil being less efficacious towards the vaccines. The way to kind of look at it is there's different aspects that have been affected by the mutations of each of the variants. In regards to the B1351 and the P1 variants, the difference between that and the B117 is there's an extra mutation that carries, and that is called the E484K mutation. And what that has done is it's actually impacted the actual spike protein, which is being used for the vaccines to develop those neutralizing antibodies in the body, right? And so what that does is it actually decreases the ability for the vaccine sera, or the antibodies from natural immunity, to recognize that spike on that virus.

Aisha Khatib: And so you almost have a bit of what we call an immune escape or an immune evasion. Now what we do know is that from the P1 and the B1351, that it's not an all or nothing, right? So we've seen that yes, it decreases the effectiveness of the vaccine, in particular to those two variants. As we've seen for the B117, that actually has not been the case. And the B117 actually, is still quite efficacious with the vaccine. But even for the other two variants, the efficacy to neutralize those antibodies, which are able to then kind of recognize the spike proteins isn't an all-or-nothing thing. There's a decrease in it, but that decrease is still not potentially enough to not protect you. You're still going to get that partial protection from the vaccination.

Aisha Khatib: And also, the other thing to look at is these vaccinations are, if you look at the immunogenicity and the effectiveness, you're looking at 95 percent effectiveness. Even if that effectiveness drops down to 70 percent, that's still going to provide protection in the community. And another thing to think about is that vaccination, it's not a therapy directed for the disease specifically. It's actually a public health intervention. And it's really to understand these vaccines as not a disease-specific therapy, but a public health intervention to protect the masses. And by vaccinating as many people as possible, what you're going to be doing is you're going to have less symptoms, therefore less transmission, less infectiousness, and then you're going to have less virus circulating, and then you're going to have less variants that can actually come out of those viruses circulating, and so you have more likely to return to normal.

Aisha Khatib: And so really, it is a race to get as many people vaccinated as possible as fast as possible, so that we decrease the chance of new variants emerging that could potentially have more of an immune evasion from these vaccines.

Peter Nord: So it sounds like a win-win. The vaccination, even with the variants, it's a win for the individual, because they're going to be less sick, and it's a win for the population. And ultimately leading towards that air quotes "herd immunity" that we can sometimes talk about. We've got some research on the B117, that it's significantly more deadly than the previous dominant strain that we were seeing here. Why does it have a high mortality rate, and what makes the new variants more dangerous than the original strain that we were seeing here in Canada?

Aisha Khatib: Yeah, so the studies coming out in regards to looking at the actual pathogenicity of the B117, they're not concrete yet. And so one of the things that we're seeing with the B117 is, because there's up to 50 percent more transmission, you're actually getting more people infected. And just by the sheer numbers of people being infected, you're going to have increased severe disease, and you're going to have increased numbers of mortality, if you look at the stats of the proportion of people who get severe disease versus those that don't. So there are some studies kind of looking at the severity of disease and increased mortality. And some studies coming out are saying, yes, it might be about 30 percent more, although that again, those have been limited in studies, so we don't actually have concrete evidence at this point to really prove that. And also, the actual mechanism of that is still kind of questionable. And that's still being kind of researched. There's still a lot we don't know.

Aisha Khatib: And that's also the thing that's concerning, is that we don't know a lot about this. And what we do know, though, is how we potentially can protect us is to decrease that transmission. And so those who are more vulnerable to potentially having more severe disease, it's even more important that those people continue to try to mitigate their risk until they can get vaccinated, and when the opportunity arises to get vaccinated, that they do get vaccinated.

Peter Nord: So it's sort of the rate versus the absolute numbers. We have to just wait. The numbers aren't in officially, but we'll be looking for those studies to give us that information. But I know that's something that people were looking at the increased mortality rates, and thinking well, clearly the variants are a worse virus than the original strain. And it's just because of the transmissibility the pool is bigger, so the absolute numbers are certainly higher. And that's mortality. But what about symptoms? There's questions around whether the new variants present worsening symptoms short of actually being admitted to hospital or in the ICU or even dying. Have we seen anything that would suggest that B117 in particular produces any worse symptoms than the current strain?

Aisha Khatib: Currently, no. There's no evidence to actually show that there are more severe symptoms from the B117. We definitely are seeing more symptomatic people come through the assessment centre, and there are some early studies saying that around 30 percent, there might be increased severity. But again, these are limited studies, and there hasn't been anything that's concrete at this point.

Peter Nord: And I guess along the same lines, is there any way for a person to know that they might be infected with the variant versus the regular strain? And I'm guessing no.

Aisha Khatib: So we are actually testing for the variants. Basically, if you come into the assessment centre and you test positive, we call back those positive cases. And on that positive sheet, it'll indicate to us that there is a variant of concern that has been detected. Now the problem is that there's a mutation for these variants. It's the N501Y. And I have to remember all these letters. But that variant is basically the one that increases the receptor binding and increases transmission. So that is picked up pretty quickly actually, on a positive case. Those positives are then taken and they need to be sequenced. So the entire genome, the genetic code, is then sequenced for those, but that can take up to three weeks. So we do get those results back. The person who has been called to say, "Hey, you're positive and you need to isolate. We think that this may be a variant." It's been flagged as a variant, but we won't know what variant it is yet for a few weeks. So they may know that they have a variant, but they may not know which variant just yet because it takes that long to process.

Aisha Khatib: Now if you look across Canada, we have about 3,000 variants of concerns that have been identified. Within Ontario, it's almost 1,000—about 950 of those have been B117. Less than 20 of those have been P1 and the rest the B1351. However, on the backlog is about 6,500 cases that have been identified as variants on these positive cases. They have been identified as variants of concern, and we just don't know which variants of concern yet because of the fact that it takes so long to sequence them. Now that's a concern, right? That's an issue because likely we are underreporting what's happening in the community. So if we're saying 40 to 41 percent of cases are these variants, it's likely higher. And on top of that, maybe we're not detecting them as well because we're probably not getting that sample size of potential variants.

Peter Nord: So it's a real lag indicator, then. I guess the other aspect is, for all the positive cases that are coming back, are they all being checked for variants? Or are they doing a sample? Is it a statistically significant sample that they're taking? Or is it everybody who's coming back positive is having their genome sequenced?

Aisha Khatib: So in Canada, it's about five percent of the positives that are being sampled and sequenced. Obviously, there's certain characteristics that we'll flag and that we'll automatically have them sequenced. So for example, if you've travelled, if you've been a return traveller and you're positive. If you have been vaccinated and you come back positive. If you have been reinfected, then that's another reason that you'll be flagged. So there's certain criteria that kind of fall within those sampling for that five percent. And we're also seeing other variants of concern pop up in different places. So there's another one that's just come up in New York, there's one in California, and now we're hearing about one in Nigeria. So they're region specific, and so it's really important to be monitoring for that. And there's surveillance happening across the world in regards to these different variants that potentially could become a challenge against the vaccines in particular.

Peter Nord: So thinking about the future look, looking into your crystal ball a little bit, do you think we're going to see more of these variants of concern here in Canada?

Aisha Khatib: I think as long as we have viruses circulating, new infections and transmission happening, there's always risk of a new mutation and a new variant. And remember, these are very advantageous viruses trying to propagate themselves. And so there may be a new variant, and that perhaps may become a challenge for us in the sense that it will either decrease vaccine effectiveness, or present in a more challenging way.

Aisha Khatib: I think one of the other things that you discuss is yes, these travel bans. And what's really important to kind of look at from that perspective is the global vaccine inequity. Even if we get one country or two countries fully vaccinated, the problem is that you can have these variants emerge regionally, right? And unless that country is getting their population vaccinated at the same time, it can become an issue and a threat to another country's population who may already have those vaccines on board. So I think there really needs to be a concerted global effort here to really try to decrease that global transmission and really getting these vaccines out there to, like, the most vulnerable populations. And to really also rally the public and rally everybody to do their concerted effort into rolling up their sleeve to get vaccinated, because that's actually going to make a huge difference to decrease transmission. But while you're waiting for that, keep on tightening up your public health mitigation measures. I know it's hard for people, but we need to keep masking, we need to keep distancing, we need to keep washing our hands until we can get as many people vaccinated. And how tragic would it be if we start relaxing now when we're kind of staring down the barrel of a third wave with these variants. So that's the concern, and that's the urgency that we're feeling right now. It's definitely a public health emergency we're dealing with.

Peter Nord: Yeah, no question. And the fact is, the vaccines are incredible and core to tamping down this pandemic here at home and globally. And the fact is, we don't really know how long an individual's immune response lasts after that vaccination. And so if there is this asynchronous approach globally, does it make sense that we're going to be looking towards booster shots in the future to try and keep ahead of this asynchronous vaccination approach across the globe?

Aisha Khatib: I think there definitely will be boosters that are required. I know Pfizer and Moderna are looking—I think Pfizer's looking at one about six to 12 months out right now that they're developing. So it's definitely being looked at. And the nice thing is that there's a lot of background and foundation that's made for these vaccines. So it's actually relatively—I'm not going to say it's very easy, but it's actually quite easy to tinker the vaccines to accommodate for these variants if needed to create these booster shots as needed. So that's kind of a reassuring thing as well, is if we need to have those boosters to accommodate for various vaccines or different strains or to have multiple variants covered by these shots, that's going to be a possibility. And that's something that's coming down the line for sure.

Peter Nord: Yeah, and speaking with the folks from Moderna, they've said they can retool their vaccine, the recipe, and within six weeks, they could be producing a whole new vaccine. Not entirely new, but enough new to go after the predominant strain, whether that's in a region or in a specific time period. Eventually, we might end up with that Influenza A, B, and C for COVID shot on an annual basis.

Aisha Khatib: Yeah. So that's fantastic, yeah.

Peter Nord: Yeah, that'd be terrific. So last question—and you mentioned the third wave, and that's a real concern for a lot of people. So what about that? What is the chance of a third wave? And how did the variants play into that?

Aisha Khatib: So if you look at the projections that have been done by a lot of very, very smart people who've been following COVID and the way these waves have kind of come and gone, I think it's a reality that we're facing. And it almost feels like we've already started. We're starting to see a slight trend up in cases. The concern is that these variants spread quickly, and we're going to see more numbers. And I think the third wave that we see is going to be predominantly borne by variants of concern. But I think we really need to be aware that we are in a very kind of precarious situation right now, where these variants can get out of control very, very fast. And I think the concern is that we're already at 40 percent, and with a reproductive number of 1.29 that these numbers are going to creep up very, very fast. And they're projecting the third wave probably in the next few weeks to early April, where we could potentially be seeing anywhere between 5,000 to 8,000 cases a day.

Peter Nord: Yeah, that would be a bit ominous. But I think we're also obviously cautiously optimistic that getting these shots in people's arms is going to make a little dent in that. And hopefully, as we see those case counts go up, fingers crossed that there's enough vaccination going on that those hospitalization, the ICU rates, the ventilator rates, the mortality rates, are tamped down a little bit by vaccinating the most high-risk populations as quickly as we can. So hopefully, that'll be one silver lining to a third wave. Never good, but hopefully less mortality associated with the third wave than compared to the previous two waves. So this has been super interesting. I know I've learned lots here today. I know our listeners are fascinated by hearing this because it's such a topic of interest right now. Dr. Khatib, thank you so much for your time today.

Aisha Khatib: Thank you so much for having me. And let's do our part and roll up our sleeves and get vaccinated as fast as we can.

Christopher Shulgan: And that's it for the conversation between Medcan chief medical officer Dr. Peter Nord and the clinical director of travel medicine, Dr. Aisha Khatib. Find Dr. Khatib on Twitter @aishakhatib.

Christopher Shulgan: I'm executive producer Christopher Shulgan. For those seeking to learn more about variants and COVID, we'll post links and episode highlights at eatmovethinkpodcast.com.

Christopher Shulgan: Eat Move Think is produced by Ghost Bureau. Senior producer is Russell Gragg. Editorial and social media support from Chantel Guertin, Emily Mannella and Tiffany Lewis.

Christopher Shulgan: Remember to rate and subscribe to Eat Move Think on your favourite podcast platform. Follow our host Shaun Francis on Twitter and Instagram @Shauncfrancis—that's Shaun with a U—and Medcan @medcanlivewell. We'll be back soon with a new episode examining the latest in health and wellness.

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