Coronapod: Variants – what you need to know

Benjamin Thompson

Welcome to Coronapod.

Noah Baker

In this show, we’re going to bring you Nature’s take on the latest COVID-19 developments.

Benjamin Thompson

And we’ll be speaking to experts around the world about research during the pandemic.

Amy Maxmen

We’re entering a new era now. We have new COVID strategies, there’s some new unknowns and we’ve got a vaccine.

Benjamin Thompson

Hi, listeners, Benjamin here, coming to you from the South London basement once again. Welcome to this week’s edition of Coronapod, and joining me once more are Noah Baker and Amy Maxmen. Hello to you both.

Amy Maxmen

Hi, good morning.

Noah Baker

Hi, Ben.

Benjamin Thompson

Today we’re going to be talking about things that have been receiving a lot of coverage recently and are causing a fair bit of concern in some quarters, and they are virus variants. I think we should maybe start the show by defining what we mean by a ‘variant’ because it’s a fairly ambiguous word in some circles. Who would like to take that one?

Noah Baker

I can probably jump in on that one. So, there’s been a lot of discussion over how we should refer to these variants. Words like ‘strain’ have been thrown around, ‘variant’ has been thrown around, and it means a whole bunch of different things. Essentially, when we talk about a variant of a virus, we’re talking about some mutations in the genome of that virus, and those mutations could have no effect at all, those mutations could however have a functional change, and the ones that we’re going to be talking about here are variants that have been shown to somehow change the way that the virus, the SARS-CoV-2 virus in this case, interacts with people or spreads or even its lethality, how dangerous it could be, and those variants around the world are causing quite significant concern. There are questions like how might variants in the virus change the way that vaccines work, how might they change natural immunity, whether or not people might be immune to a new variant of a virus, and I guess these are some of the things we can start to dig into while talking about variants in this Coronapod.

Benjamin Thompson

And there are two of these variants in particular that are being studied pretty heavily then and they have, well, quite particular names.

Amy Maxmen

So, I think maybe the first one that we all heard about was the one that was detected in the UK – B1.1.7 – and I think maybe the first news about that one was that it’s more transmissible according to several lines of evidence. And then there was a second one that was detected in South Africa, and it’s really swept through South Africa. The last thing I read is that it’s now 90% of the cases in South Africa are this variant. It’s also called 501Y.V2 or B1351, and now it’s spread to 31 countries. I mean, of course, those are the places we know about. The one that was detected in the UK is in 73 countries. And maybe we want to make a note about naming. Yesterday, the WHO had a press briefing where they sort of noted we need to think of new ways to name these variants because we don’t want to name them after the country where they were detected. That’s kind of misleading because people think, ‘Let’s just block off South Africa,’ or something like that, so it’s misleading, leads to the wrong behaviour, can be stigmatising. There’s like a few reasons why we don’t want to name it after the country. But then again, saying something like 50Y1.V2, I know even for me, you give me a few of those and I’m going to start to get confused.

Noah Baker

Absolutely. I think even beyond that, if you think about the countries where they’re first detected, that doesn’t mean that’s the country where the mutation first happened either, right? So, for example, the UK has a really active genomic surveillance system running that is really world-leading. In fact, currently almost half of the SARS-CoV-2 genomes that have been uploaded to GISAID, which is a not-for-profit collection of genomes that are collected and collated, almost half of those have come from the UK. And so, when you have some countries that are really over-sampling and others that are under-sampling then you’re going to pick up variants in one place more than you might in another place, and so I think it’s really key to make sure that we think about naming these things in the correct way because scientifically and morally and even just in terms of memory, there’s a lot of things to think about there.

Amy Maxmen

Yeah, for sure. And so, the latest news, I think, that was interesting is that the variant that was first picked up in South Africa, this 501Y.V2, so this is the one that has a mutation in its spike protein – that’s the protein that it uses to enter cells – it has this mutation called E484K. So, there’s this particular mutation in the spike protein and so that one, they’ve noticed that antibodies that are, say, generated against the original coronavirus might miss this new variant because of the changes on this spike protein. So, that means two things. One, it’s been found that people who already had COVID could be reinfected with this variant. The other thing it means is that the vaccines that have been made, where they were designed with the original spike protein in mind, those vaccines might be less effective against this variant. But here’s the kind of latest news on top of that. That’s what was worrying be about the one that was detected in South Africa, this mutation E484K. But now in the UK, the variant that we saw there, B1.1.7, I think at least 16 variations on that variant have been seen and some of them have this mutation E484K.

Benjamin Thompson

Yeah, two big questions there, and this is what researchers are really trying to get to the bottom of. Now, from what I understand in terms of whether this mutation will affect vaccine efficacy, results have shown that that may well be the case, but it doesn’t appear to have gone from an ‘it works’ to an ‘it doesn’t work’ situation. There’s not this kind of binary on or off, but there may be a reduction in how well a vaccine works, and I think in one of our stories we’ve got some numbers showing how that might play out for a new vaccine that’s had a phase III trial.

Amy Maxmen

Yes, that’s very true. So far, everything seems to still have some efficacy. The vaccine from Johnson & Johnson, it’s a single shot adenovirus vector vaccine, so that means basically they stuffed something that was made in the lab that looks like the spike protein into a cold virus vector that’s been inactivated that shuttles the spike protein into a cell. So, the Johnson & Johnson vaccine, in a trial, it was 66% overall against moderate to severe COVID, but when you divide that up by the countries that it was tested, it was actually 72% effective in the US and yet 57% effective in South Africa where we assume that’s been brought down because of the variant that’s there.

Noah Baker

I think it’s so difficult when we think about how variants might interact with immune response, might interact with vaccine responses, because there are so many moving parts here, and really a lot of this can come down to apples and oranges. So, there are limitless combinations of variants you could have. You could also have two of these variants could end up in one virus particle which could change the dynamics again. And then the way they impact the immune response is also variable, so the immune response isn’t just a case of the virus arrives and there’s an immune response. The immune response is made up of a whole bunch of different responses. There’s T-cell inactivation, there’s various types of antibody responses, some are neutralising, some are not. And all these variants could cause changes in all of these different types of immune response in different scenarios, and so it’s very, very hard to really nail how variants are going to impact immunity or impact the efficacy of vaccines in any kind of firm way, but it is certainly enough to cause concern around the world, and that’s leading people to ask questions like, ‘Do we need new vaccines already?’ And that’s kind of a whole other topic of conversation to discuss.

Amy Maxmen

Yeah, the vaccine manufacturers are really thinking we were seeing these great numbers, upwards of 90% for a lot of the vaccines, but if they’re brought down already by the variants that we know exist now, what could happen as new combinations of mutations arise? So, this is something manufacturers are thinking about. I think Moderna, which has one of the mRNA vaccines, they’re already talking about can they reformulate theirs so that not only does it sort of mimic properties of the spike protein in the original coronavirus but also mimic properties of the spike protein in 50Y1.V2, that’s the one that was originally found in South Africa.

Benjamin Thompson

Yeah, the team behind the Oxford-AstraZeneca vaccine have come out today, I believe, and said they’re looking to reformulate theirs and have a new version of the vaccine ready by Autumn, from what’s been reported. So, yeah, it seems like companies are jumping into action.

Noah Baker

I think as well it’s probably worth mentioning that although vaccine manufacturers are looking at ways to update their vaccine or create new vaccines or new formulations of the vaccine, there is a source in one of Nature’s stories this week written by our colleague Ewen Callaway that says those things are important, but really the biggest tool we have here and the most powerful tool we have here Is deploying the vaccines we already have as quickly as possible. If we can quash as much as we can before new variants take hold too much then that severely restricts the ability of new variants to take hold any further, if that makes sense. Amy, I do have another question for you though, right, because from your experience, this pandemic has happened and it started and there was immediately things you could do. There was a kind of century-old playbook of public health response which was contact trace, test, isolate, so on and so on. And then vaccines were being developed and it was done incredibly quickly this time using these amazing new technologies, but there was kind of a playbook about how to do that as well, and it was sped up and it was great, but we didn’t hear the word variant in the news until like a couple of months ago, and yet surely it’s also part of that same playbook, that variants are coming, right? Viruses are going to mutate. That’s what they do. We’ve known that for a very long time. Is this something that you’re surprised is only coming up now or have you seen people kind of not thinking about this step before in pandemics or in public health responses that you’ve covered?

Amy Maxmen

I think anybody who studies evolutionary biology would have known that this is coming. I mean, early on there were researchers, and we talked about the group Nextstrain a while back. They compare sort of people who post their genome sequences to this online resource that you mentioned earlier. So, they compare genomes and they sort of make family trees of the virus’ genomes to see how it’s changing over time. So, already they have been watching this enough to know, okay, this virus isn’t mutating especially rapidly. It’s not slow. It’s not fast. It’s sort of moderate, what you would expect. I think that’s one thing to make clear. So, I think they’ve definitely had their radar up. As for like was it really in, say, December or something when the first variant that had an effect on functionality was detected? I think, if you remember, there were variants detected earlier last year but the studies showing whether or not they were more lethal or more transmissible were kind of inconclusive. I think we had a peak of headlines like, ‘Deadly new variant,’ but those are really hard studies to prove because you don’t want to just show something in a petri dish. You kind of also want to see do we have signs saying is this sweeping through the population, things like that, so maybe it just took a while to have the accumulation of evidence there to say, ‘No, for sure this is definitely more transmissible than what we saw before.’ But to your point, I think back then, there were definitely people who were saying, ‘We really should be moving on this,’ because the more virus you have, the more chances that some of those viruses are going to spontaneously have mutations that are helpful to their survival and worse for our survival, so by all means let’s try and contain this before that happens because speed is important. I completely agree with what Ewen said in his story. The best thing to do right now would be to get those vaccines out there, and I also want to say to get them out there to communities that are really hit hard by the virus because we can really get them out there to people who live pretty isolated lives like myself, but that’s not really going to change how fast this thing is spreading. We really need to get it to the places where there’s a ton of virus. That makes sense because those are going to be the places where the virus has the most chance of mutating.

Noah Baker

Absolutely, and I think it’s easy for me to sit here going, ‘Oh, god, I’ve only just started seeing the word ‘variant’ in the news and surely we’ve always known that was going to happen,’ but I guess we should also remember that eight months ago there wasn’t a single working vaccine and so to be expecting them to be coming up with variant vaccines as well in the space of a year maybe is asking quite a lot of scientists. It’s not that they weren’t thinking about it, it’s just that there’s only so much that a news cycle can handle.

Amy Maxmen

Yeah, for sure. I mean, I remember early on talking with a researcher in Nigeria who was doing some sequencing of the virus in his lab. They were one of the only labs on the continent of Africa doing whole genome sequencing of the virus, and he was saying, ‘This is so important because we need to know what are the variants of the virus that are circulating here because that’s going to matter when it comes to figuring out what vaccines to use.

Noah Baker

I think these recent developments with variants are really bringing into focus the value of genomic surveillance. I think there was a source in one of our stories that was quoted as saying, ‘It’s really kind of come of age as a discipline during this pandemic,’ and that is just sampling the virus that’s found in different populations and sequencing the genome and getting it uploaded to a place where it can be shared and compared because that’s really the way we’ve been tracking these things. And as time goes on, I feel like tracking how this virus is mutating around the world is going to become more and more vital to finally winning the battle, as it were.

Amy Maxmen

Yeah, for sure, It’s really important. There’s so many things about this outbreak where you’re like living in déjà vu from 2020, and it’s disappointing that the US doesn’t have a system for this yet because so many labs can do whole genome sequencing for viruses. It’s not that we don’t have the capability, but it really needs a system. We need to have it so that some certain percent, let’s say, I think I’ve seen the number thrown around that at least 5% of coronavirus cases, that virus should be sequenced. So, it really involves making a sort of system where, say, health departments work with labs, whether that’s private sector or academia, to make sure that we’re sequencing these variants and uploading them to a site where people analyse them. And I guess it’s worth saying the US has identified these variants we’ve talked about. They’ve all now been found in the US. They don’t seem to be particularly common but then again it’s not like we’re sequencing a lot and who knows what else is here.

Noah Baker

And I guess it’s important to mention that those that have been found in the US, that some of them have also been found in the UK. That doesn’t necessarily mean people have travelled from South Africa or wherever it is. Those variants can also arise because viruses mutate and the mutations that stick in a population could be the same mutation in different places.

Amy Maxmen

Yeah, there could be independent evolution. That’s something else that phylogeneticists also look at, and they do that by saying, ‘Okay, what’s the background?’ If they have the whole genome they can say, ‘Are they exactly this one that we found in the UK and this one that we found in Kansas? Are they exactly the same or are there reasons to believe that they arose independently because the backgrounds are a little bit different?’

Noah Baker

It’s the sort of hard science angle which I think people could easily overlook as being important when they’re focusing on diagnostic testing and treatment and so on and developing vaccines. This sort of surveillance, this sort of genomic sequencing for surveillance and gathering data, maybe is easy for people to sort of sweep under the rug as somehow less important, but it’s not. It’s really, really vital. I also wonder whether or not, as well as having systems in place in countries, it would also be really useful to have a kind of globally organised system through some kind of organisation like the WHO, which could help properly survey the different variants in different countries around the world.

Amy Maxmen

Yeah, for sure, and that’s something they did speak about at their last press briefing as well. They were saying we need to have kind of a collective database for this sort of thing and they also want to think of what are smarter ways to be naming it, so that’s something that’s certainly on their mind. There’s also been a lot of talk, given these variants, Dr Tedros at the WHO had an editorial yesterday out where he notes that most of the world’s vaccine supply has gone to wealthy countries that house 16% of the world’s population, and meanwhile all of these middle-income and low-income countries are really without vaccines. And so, he talked about a moral obligation, and I can see that angle being really strong, especially thinking about healthcare workers in those places. Some countries have less 20 times fewer nurses than we do in the UK or in the US, so the idea of having a virus that’s going to threaten the lives of a lot of health workers in places where there’s very few health workers is devastating. But I guess the news with the variants also makes it a sort of practical obligation. If you want to go ahead and let this virus just thrive in other countries, just very practically that’s also going to give it time to mutate and have more variants there, so there’s sort of a dual reason why there really should be a huge push to get the vaccine to other countries, and whether that’s with donations or changes in patents or setting up and making sure that manufacturers can allow generic manufacturers to make the vaccine. All of that is really important to push on.

Benjamin Thompson

Well, the issue of vaccine manufacture and rollout is a huge one, Amy, as you’ve just touched on there, and definitely something that we’ll have to talk about in future. But let’s leave it there for this week’s Coronapod. Noah and Amy, thank you as always for joining me.

Amy Maxmen

Thank you.

Noah Baker

Thanks, Amy. Thanks, Ben.