Hello, and thank you for listening to the MicroBinFeed podcast. Here, we will be
discussing topics in microbial bioinformatics. We hope that we can give you some
insights, tips, and tricks along the way. There's so much information we all
know from working in the field, but nobody writes it down. There is no manual,
and it's assumed you'll pick it up. We hope to fill in a few of these gaps. My
co-hosts are Dr. Nabil Ali Khan and Dr. Andrew Page. I am Dr. Lee Katz. Both
Andrew and Nabil work in the Quadram Institute in Norwich, UK, where they work
on microbes in food and the impact on human health. I work at Centers for
Disease Control and Prevention and am an adjunct member at the University of
Georgia in the U.S. I'm joined today by Niamh Tumulty, who is the Head of
Research Services and STEM Libraries at the University of Cambridge. So Niamh
and I were having a chat the other day about new variants, and there seemed to
be a little bit of confusion. So we thought that we'd talk today and maybe try
and clear some of this up. Thanks for having me along, Andrew. So to start,
maybe tell me a little bit about the level of change you see normally when
you're doing genomic analysis. You know, for the first however many months of
the work you were doing, you were always seeing a certain amount of variation in
the genome, but you weren't calling them new variants. What was that level of
what you were seeing before? So over the past year, what we've been seeing is
changes happen in the genome all the time, normally at about a rate of about two
changes a month. And it's been, you know, quite like clockwork. And we've been
using these changes to track the spread of different lineages throughout the
world. So there have been cases where particular lineages, so that is something
that's genetically distinct, have popped up. Over the summer, the incidence of
coronavirus was very low in the UK. And then everyone went on their summer
holidays, and then they brought back lineages which were circulating in Europe.
So in particular, there's one which was first identified in Spanish agricultural
workers, and then it spread to the local community, and then it spread to
tourists, and then it spread to other countries. And then that became the
dominant lineage in the UK. And in September, October, November, it was, you
know, accounting for virtually all of the cases. So you've been talking about a
normal level of change, you've been talking about different lineages that
already existed in different places. Why are people now talking about variants
rather than lineages? And what exactly is the difference between a variant and a
different lineage? My God, I mean, there is huge confusion over a lineage, a
variant, a strain. And they're not, you know, like super well defined. So
there's a bit of wiggle room and fuzziness, and everyone is confused. So
generally, by normal people, they're interchangeably used, even by people in the
field. It's confusing. What we use quite a bit is lineage. And that's because we
want to look at clusters of genomes, and then use that for genomic epidemiology.
So saying, is something similar or different? Where it gets confusing then is
where you have a lot of changes, and you want to get across that, you know,
something is maybe concerning. And that's where the name new variant has come
from. So at what point does it stop just being a different lineage? And at what
point do you decide to start calling it a new variant instead? That's a very
difficult question. And it came about because Public Health England said, we
have a variant under investigation. And they gave an ID number. So it's VUI
2020-12-01, because that was the month and the year, and I was the first one
identified in that month. So you know, nice name and convention, a bit of a
mouthful, but nice name and convention. And that's where then the word variant
came up. And people then started getting excited about it, particularly when the
Minister for Health stood up and said, you know, this is a problem. And at that
point, there's only one of them being talked about. But now we have about four
of them at least, and there's probably going to be more every day. And there's
different competing trains of thought. Some people would say, you need to define
a constellation of changes, which may arise independently throughout the world.
And that's kind of what we're seeing now. We're seeing similar changes in
similar parts of the genomes arising totally independently in different parts of
the world. And that's obviously because it gives some kind of advantage to the
virus. So it might help it spread, or it might help it evade the immune system,
that kind of thing. And these independent changes, then it makes the virus in
some way fitter, and it lets it spread more. So as genome sequencing ramps up
around the world, we're going to see more of these. We're also going to see a
lot of panic, where people have a look through their data, and they find, oh,
I've got a change here, it looks interesting. And then suddenly, you know, you
have this big, huge, you know, news flash saying, oh, we've got another variant,
and it's causing, you know, all these problems, or it might, you know, cause the
end of the world. Well, you know, we don't know. In terms of lineage, then,
that's for phylogenetics, and it's just a way of kind of categorizing things
loosely and saying, well, these are similar, these are similar, and it's
shorthand for what's similar, what's different. So do you think, then, that
people are going to start saying variant where two months ago they would have
just said new lineage? Yeah. So this is really confusing, okay? So if you take
what we have in the UK, first of all, it was VUI 2020-1201, then it became
variant of concern when they did a bit more investigation, so then it's VOC
2020-1201. Referring to the same thing. Yeah, the same thing. Then the press was
calling it the Kent variant, or the UK variant, or initially it's just the new
variant, and I'm doing air quotes here, which obviously doesn't translate to
podcasting, but there you go. And then you have another group who have a
different naming scheme, and they said it was like 20I slash 501Y dot V1, right?
Just to deconstruct that, the first 20 is like the year, and then I is like the
hurricane naming scheme, you know, where you give big events, you know, these
individual letters, and then 501Y is this major change that people think is
linked to increased transmission, and then V1 means it was like the first one
found, and that's great, but then you have also a lineage name, which is decided
by Olly Pivas' group, and that's B1.1.7. So you're saying there's a whole load
of different names for the exact same thing? Yeah, it's really confusing, and so
often I am, you know, when I'm communicating with people I'll put in like three
or four different identifiers because I don't know which one they're actually
using themselves, so it gets super complicated super quick. But where it gets
even more complicated is that as people started looking into this stuff more,
and they've found particular concerning patterns, we've found more and more of
these variants that people think are concerning, and so South Africa, Etulio de
Oliveira came up and with their sequencing, they found that actually there was a
rapidly spreading lineage down there, and they found that actually it had a
similar mutation to one that was in the UK. It arose independently, but similar.
Of course, they were smart, and they made sure not to have their country's name
associated with that variant, and so it's now, it was called 501Y.V2, because
it's the second time this particular mutation was identified as a concern, but
we call it as well B.1.351, and basically everyone's calling it, you know, lots
of different things. Let me stop you there. So I'm a librarian, and I'm
thinking, I'm listening to all of this, and I'm thinking oh my god, how much
more confusion could you create by labelling the exact same thing so many
different ways? Why? Why do they label them all differently? I don't understand
why they don't pick one and then call it that. Why have so many different ones?
It's pandemic, and everyone is doing things very rapidly. Things are changing.
There's no rules properly set for this particular virus, and so different groups
in different parts of the world are labelling it slightly differently. Some
people are looking at just the phylogenetic, some people are looking at things
that are concerning, and it gets very confusing very quickly. Even people in the
field don't understand most of this, and I only have a passing grasp on it.
Well, because I thought metadata of this sort was very well established in that
field, so that's what's fascinating to me, that obviously what's been working
reasonably well in a normal pattern seems to be falling apart a little bit when
it comes to, midst of a pandemic, when these changes are happening.  happening
so rapidly. Obviously all the different possible ways of naming things are being
used instantly to mean the same, to apply to the same thing. Yeah these names
are being pumped out very rapidly and you know often within a few hours of a
notice going out they'll have to label it so that the press and everyone can
convey that this is the thing we're talking about because it gets so confusing
so quickly. The WHO are trying to I suppose get some normality there and bring
people together but obviously you know it's so complicated. So within the field
people are now talking about constellations of mutations and that just makes the
names a little bit even worse because now you're not just talking about a few
letters and numbers you might be talking about you know three or four different
mutations tacked on to something else and it can get very confusing to convey
this information very quickly and so I suppose there is a need for shorthand
with this. And you can see why the media so quickly starts calling it the Kent
variant or the South African variant or the one from Brazil. So we have to say
that we're recording this on the 16th of January and that's very important
because this stuff changes every day. Only yesterday there was confusion over
Brazilian variants. Because you were saying there were two Brazilian variants.
Well obviously there are many changes as we've established already. There are
many different lineages but there are two Brazilian variants that are currently
being looked at. This is where it gets confusing because a Japanese group
identified in Brazilian travellers that there was you know some serious changes
that looked really bad and they sequenced them and they made it public and that
was just last weekend and then there was no real data. There's very little data.
It took time for it to come out. By that time then more groups released data
from Brazil and people got really really confused at that point. So there are
two interesting lineages or there are two interesting variants now labelled P1
and P2 to make things a little bit easier. So P1 is the one that people are most
concerned about. There are loads of changes and particularly with E484 and that
is the one that people are panicking about and that's in Amazonia. Is it
Manassas? Manassas isn't it? Yes and so that's where they're really concerned.
There have been no cases as of last night in the UK of that type but there have
been cases of a similar one with a similar history but without most of the
mutations and that just has you know one of these particular mutations rather
than you know a whole you know bucket loaded of them. And that's the one that is
in the UK? That's the one that definitely is in the UK because I've looked at
and found it in our own data in the east of England and I've verified the
mutations manually because you know you have to triple check this stuff before
you go and tell clinicians there's a problem. And unfortunately the media picked
things up incorrectly and so then there's lots of hype for a few minutes over
something that didn't really exist and it was just that there was confusion over
naming and so we have a crisis of naming variants of concern in the world. This
must be incredibly challenging to manage because the research is all happening
so fast there is understandably global interest in what's going on. People want
answers. I know you've had phone calls asking you to give a comment on something
that you'd heard about three minutes beforehand. It's not really surprising that
the message gets twisted at times. Yeah like last weekend I had a journalist on
asking what's going on with this Brazilian lineage. I shouldn't call it
Brazilian lineage because that's confusing. But anyway at that time there was
only one people were interested in which is P1 and that like we're basing
everything off like a screenshot of a tweet and that someone had translated from
Japanese into English. We were using Google Translate. Luckily someone in my
group speaks Japanese and then you know we're basing it off that and then
there's no data available in GISAID at all at that point. You know being
deposited takes time and so everyone was trying to base things off like partial
information and it took you know another day or two for stuff to actually get
out there and be released and be analyzed by people actually know what they're
doing. And so then there are two posts on virological kind of competing posts
actually by Brazilian groups and that really cleared it up. Certainly one would
I think it's a CADE project who had done Zika sequencing you know really did
clear a lot of that up and you know said okay this is what's going on. These are
mutations. This is how we're going to bring it under control. Yeah. But it is
confusing and I know that next week we're probably going to have more like these
they seem to be popping up like mushrooms you know there's going to be a load
more you know when we wake up. Well yeah especially as we say people start
calling every new lineage a new variant. It's yeah the media's at some point
they're going to burn out though and stop being so interested in all these new
variants. God only knows. Hopefully quite quickly. But then you know you're
going to be getting into delving into problematic areas very rapidly like you
had in the US. Trump was talking about the China flu. That's why when naming
these kind of things you want to get away from country names because you don't
want to stigmatize things like Spanish flu and this kind of thing. They can
stick around for a long time. Yeah. So you've got to be very very careful about
it. So one of the things I suppose we should talk about is how worried we should
be about all of these different variants and it sounds like the answer is
increased transmissibility in the sorry can't call it the UK variant B.1.1.7
whatever it is. Sure. So the increased transmissibility is a concern even if the
symptoms after it's been transmitted are similar to what was already there
purely because if it's being transmitted more quickly then there will be more
people having all of these symptoms in the full range from mild barely know
you're ill through to mortality. With the other variants do we have any sense of
what's going on with them what effect these clusters of mutations are having on
those particular variants. This is a problem right because things happen so
quick that people haven't had enough time to properly study the actual variants
in the impact and you know that takes a lot of time. It takes scientists in a
lab quite a long time so we have to look at maybe higher level things or can
make educated guesses and we don't have the luxury of having you know a year or
two years to really dig into this stuff. It has to be done like sometimes hours
or days you know people just knocking stuff out and that is a problem and
there'll be many many false alarms. We do know or we could see very clearly from
the UK variant sorry B.1.1.7 we know from that that actually it does transmit
more because during our lockdown here we could see everything else going down
and going extinct and then this one you know was just shooting up rapidly and
it's stabilised in our area in Norfolk at about 80 percent of all new cases
which is quite high like shockingly high and it's come from basically nowhere
you know. The first case in that area was maybe in mid-November you know and it
suddenly come to dominate. With the variants in other parts of the world there
is concern that maybe it changes how the antibodies work and maybe as a way to
evade and live longer in your body. Stop being killed off. So a lot of that work
is ongoing but certainly it's just going to take time for everyone to tease
things out because something might look bad in by a you know computer model but
actually maybe it isn't bad in reality or it may be it's a combination of two or
three or four different changes which make it which change how it works. Maybe
we might find that some of these changes make things better maybe it lowers
mortality maybe makes it spread more easily or give a longer infectivity period
we don't know but there can be other changes which reduce the severity of
disease. Fingers crossed for that. Luckily vaccines are coming along quite
rapidly and being deployed quite rapidly so will protect the most vulnerable
people in the population. We're not seeing any vaccine escapes yet because
obviously the vaccine hasn't been deployed widely enough but that will be the
next big thing coming up on the radar which will be vaccinated people getting
COVID and then trying to figure out what's gone wrong. That's really interesting
thank you for taking the time to tell me more about the difference between
lineages variants and so on I'll watch this space. Although after listening to
this you're probably still confused because I still am. Thank you all so much
for listening to us.  If you like this podcast, please subscribe and like us on
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like this podcast, please don't do anything! This podcast was recorded by the
Microbial Bioinformatics Group and edited by Nick Waters. The opinions expressed
here are our own and do not necessarily reflect the views of CDC or the Quadrant
Institute.