By Grant Jacobs 26/11/2021


There’s a lot of news about a new variant originally reported in southern Africa. Early signs have prompted calls for immediate precautionary blocks on travel from the region to restrict its spread. The WHO has called an emergency conference on this variant. Here’s a round-up of what we know so far.

If you’re in a hurry, and want to know my call:

Thankfully, these are not calls I have to make! But if it were me I’d (1) ensure travellers from affected and at-risk countries stay in full supported isolation for 14 days until we know more, (2) give support to the African researchers to build up the data we all need, and (3) remind people to get their vaccine.

(I suspect the formal approach is to add the affected or at-risk countries to New Zealand’s list of ‘very high risk’ countries. Our list will soon to be revised so only Papua New Guinea will be on the list.)

Israel has added South Africa, Lesotho, Botswana, Zimbabwe, Mozambique, Namibia and Eswatini to their ‘red list’ (banning travel to and from these countries), and the UK is temporarily suspending flights from these countries. Scotland has imposed self-isolation and testing.

The first genomes of this variant were identified in Botswana and then in South Africa, where there are now thought to be ~100 cases known.[1,2] One case in a traveller has been identified in Hong Kong. In the modest-sized but fast-growing outbreak of COVID-19 in the South African province of Gauteng (which includes Pretoria and Johannesburg) it is suspected perhaps 90% of cases are this new variant.[2]

Speaking at a media event today, NZ’s Deputy Prime Minister Grant Robertson says that ESR has not identified any cases of this variant coming into NZ (yet).[3]

Not a week old

We’re identifying new variants quicker than ever thanks to more widespread genome sequencing and global computational biology efforts. News on this variant is not yet a week old.

These efforts are an important contribution to managing this pandemic. Historically we’d be tracking variants in hindsight, looking back saying “what happened there?” Now we’re identifying and tracking them in near real-time. It’s something we could make better use of.

We need more data to properly call just how dangerous this variant is. It may prove to be a ‘blip’, but early signs are worrying enough some scientists are calling for a block on travel from the region to prevent spread of it.

Take this growth curve, for example (from Financial Times data analyst John Burn-Murdoch’s Twitter thread) –

That’s a steep rise in cases, but you also have to keep in mind that so far it’s a steep rise of a small(ish) number of cases in a background of not a lot else –

Early in the game new variants can spread quickly due to ‘founder effects’ where new varieties develop quickly because the immediate surrounds are relatively open to new infection. Later these new tear-aways might face competition against the resident dominant strains, in some cases ultimately being unable to compete against them and fading away.

A counterpoint might be that Delta isn’t spreading that fast there, but this new variant is.

On balance we can’t tell at this stage how it will play out, but the combination of the fast initial rise and the large number of mutations suggests it’d be wise to at least keep a very close eye on it.

More transmissible and more evasive?

There are different aspects of variants to be concerned about. One is how easily they spread, their transmissibilty. The Delta variant is more transmissible than early variants, for example.

There’s also how easy or difficult it is for the immunity derived from the current vaccines to recognise and counter the variant. One measure of this will be how often the variant is found in vaccinated people or as reinfections.

Prof Francois Balloux (director of the UCL Genetics Institute, Professor of computational biology at University College London) is quoted as saying,

I would definitely expect it to be poorly recognised by neutralising antibodies relative to Alpha or Delta,” he said. “It is difficult to predict how transmissible it may be at this stage. For the time being it should be closely monitored and analysed, but there is no reason to get overly concerned unless it starts going up in frequency in the near future.

Among other aspects are how the variant affects us once in our bodies.

What’s the name?

Currently it’s being called by its PANGO lineage name, B.1.1.529.

It won’t get a Greek letter unless it’s elevated to (at least) a variant of interest (VOI). That may not be far away: the World Health Organisation are meeting today to discuss this variant. If it is assigned a Greek letter name, it’s likely to be Nu, the thirteenth letter of the Greek alphabet, Ν or ν, as it’s the next letter after Mu, the latest WHO variant of interest assigned a Greek letter.

Here’s a pronunciation guide:

(If you don’t “get” the reference, you’re clearly not a Monty Python fan!)

Not from Delta

Previously, new variants of interest or concern were thought more likely be evolutionary variations of Delta.

That’s because Delta is so dominant in most large outbreaks. New variants tend to arise from where there is a lot of replication of the virus – basically large outbreaks.

This variant is not a derived from Delta. It has many mutations in the spike protein (more on these in the next section).

One possibility for how this variant has arisen is from a chronically ill patient, such as an untreated AIDS patient.

A small number of people have persistent infections. We know from studies on people with chronic infections that the virus keeps on evolving within them. This way they can be source of variants with many mutations, like this new variant. (Another sign of this is the presence of mutations that take several steps to get arise. In shorter infection that’s unlikely to happen.)

The mutations

It has many mutations in the spike protein, many of them uncommon. A few are associated with some new properties (from a tweet by Mia Malan) –

For now the take-away point is the number mutations (30 in the spike protein) and that many of these have previous associations with the function of the virus.

Examining the combination of mutations takes time. It’s more than just reading of observations on a table! The surroundings of the mutations matter, if they interact (or clash), and so on. We can use computer models to make some suggestions to look into, but ultimately it’ll be testing in the lab and what happens in the field that matters.

To give a little bit of a feel for it, Prof Francois Balloux remarked, “It is difficult to know what to make of the carriage of both P681H and N679K. It is a combination we see only exceptionally rarely. I suspect it is generally not ‘stable’, but it might be so, in combination with other mutations/deletions.”

Where to now?

In Africa and elsewhere where’ll be a frantic scramble of work to try get a handle on what this variant means to us.

A researcher with a similar background to mine might do molecular modelling to explore the question. Experimental researchers might take variants with each combination of amino acids at positions 681 and 679 and measure their effect on, say, infecting cells. In the field, researchers will measure what’s happening in the population.

We can all hope it’s another variant that thrives in a place with lower vaccination and not many other variants to compete against, and that with better vaccination it’ll be covered.

But then again it could be a new step up, as Delta once was.

Part of this game is trying to get ahead of the virus. Identifying new variants early gives us a chance to do that.

There are hundreds of variants really. Most never get media attention, and don’t need to. A few are sufficiently concerning that they labelled variants of interest (under investigation) or variants of concern (known to be problematic).

This one may have a bit too much media attention, but it’s scientists on the ground who called it out.

So, a tough call: do you want to act fast, or wait until you have ‘perfect’ data?[3]

Also, let’s not forget to help their researchers build this data. We all need it.

Other articles in Code for life

COVID-19 The rise and rise of Delta

COVID-19 Worried about getting your vaccine or want a simple explanation?

Loops to tie a knot in proteins?

Kumara are transgenic

Coiling bacterial DNA

Footnotes

I’m leaning heavily on other’s work in this article; this is a round-up rather than a deep dive into the science.

Many articles cover this variant. This from science magazine Nature might serve as initial follow-up reading, Heavily mutated coronavirus variant puts scientists on alert.

1. We can get some sense the scale of the wider outbreak because one of the mutations results in abnormal PCR test results. PCR tests are designed to cover this, so they don’t completely fail, but the ‘drop-out’ of one of the primer matches can be used to informally detect and count the presence of the variant. Something similar was done during in the early days of the Alpha variant.

2. Online sources suggest there may be some Australian cases. I wouldn’t rely on that just yet.

3. He [Deputy Prime Minister Grant Robertson] went on to say, “there is still some debate about the transmissibility of the variant.” He points to WHO meeting overnight, and later in the media event says “we will listen to the WHO”, which suggests that they are going to wait on the outcome of that meeting.

It’s also a useful reminder of the value of doing whole-genome sequencing on every border case, as we do in NZ. We can readily look back to see if particular types of cases have entered our borders.

He [Robertson] also said that they don’t yet have advice on travel bans by the UK and Israel, which is a bit surprising as they are being widely reported.

More questions later in today’s press release suggest they are taking a ‘we are learning’ approach. I personally would act pre-emptively on this one. It’s more than most new variants we’ve seen, and NZ doesn’t have a lot of leeway with managing what we already have.

Featured image

Atomic model of the external structure of the SARS-CoV-2.

Credits: Alexey Solodovnikov (Idea, Producer, CG, Editor), Valeria Arkhipova (Scientific Сonsultant).

Source: Wikimedia Commons (CC ASA 4.0 International)