Understanding Covid-19 variants and mutations

According to Uganda Virus Research Institute, whether the strain will have an effect on the vaccine is not yet known although research is ongoing.

The coronavirus that is now threatening the world is subtly different from the one that first emerged in China. Sars-Cov-2, the official name of the virus that causes the disease Covid-19, and continues to blaze a path of destruction across the globe, is mutating. 

The discovery of the two variants of coronavirus has triggered alarm. Scientists are racing to find out whether these variants are more transmissible or could present challenges for the Covid-19 vaccine. All viruses naturally mutate, and Sars-CoV-2 is no exception, accumulating an estimated one or two changes a month.

“Mutations are usually a chance event that will have little impact on the properties of a virus,” says Dr Lucy van Dorp, an expert in the evolution of pathogens at University College London. “The very vast majority of mutations which we observe in genomes of Sars-CoV-2 are there as passengers. They do not change the behaviour of the virus, they are just carried along,” she says. 

But every once in a while, a virus strikes lucky by mutating in a way that positively affects its ability to survive and reproduce.

“Viruses carrying these mutations can then increase in frequency due to natural selection, given the right epidemiological settings,” Dr van Dorp says.

UK Variant
There is now a frantic push to work out if this is the case for the variant first detected in the UK (B.1.1.7 or VUI-202012/01), which appears to be spreading unusually fast.

 A similar but unrelated variant has emerged in South Africa, with a small number of cases now reported in the UK. The fact both have mutations in a gene that encodes the spike protein, which the virus uses to latch on to and enter human cells, is particularly worrisome.

The UK variant has 14 mutations that cause a change in protein building blocks (amino acids) and three deletions (missing bits of genetic code). According to the World Health Organization (WHO), some may influence how fast the virus spreads.

One mutation in the spike protein (known as N501Y) has been detected in several variants, including the one from South Africa.

 Laboratory experiments suggest this mutation may help the virus bind to human cells, according to the Centres for Disease Control and Prevention (CDC).
Tests 
Sars-CoV-2 has been at the heart of an unprecedented international scientific effort since early January, when researchers in China released the first genome sequence.
Scientists have now sequenced over 250,000 Sars-CoV-2 genomes, which have been shared on open data platforms.

By taking a swab from an infected patient, the genetic code of the virus can be extracted and amplified before being “read” using a sequencer.

The string of letters, or nucleotides, allows genomes and mutations to be compared.

“It is thanks to these efforts, and UK testing laboratories, that the UK variant has been flagged so quickly as a potential cause of concern,” Dr van Dorp says.

Implications on vaccine effectiveness
A key question is whether the mutations might have implications for the effectiveness of vaccines, although many experts consider this unlikely, at least in the short term.

“This will become increasingly important as vaccines are rolled out so that any plausible candidates can be identified early, followed up and tracked. Longer-term we may be required to reassess the composition of the vaccine and its delivery strategy, so these efforts will be vital. Though for now, it is too early to say,” Dr van Dorp says.

But, while scientists have spotted thousands of mutations, or changes to the virus’s genetic material, only one has so far been singled out as possibly altering its behaviour. 

The crucial questions about this mutation are: does this make the virus more infectious - or lethal - in humans? And could it pose a threat to the success of a future vaccine?

This coronavirus is actually changing very slowly compared with a virus such as flu. With relatively low levels of natural immunity in the population, no vaccine and few effective treatments, there is no pressure on it to adapt. 

So far, it is doing a good job of keeping itself in circulation as it is. 

The notable mutation - named D614G and situated within the protein making up the virus’s “spike” it uses to break into our cells - appeared sometime after the initial Wuhan outbreak, probably in Italy. It is now seen in as many as 97 per cent of samples around the world. 
Evolutionary edge
The question is whether this dominance is the mutation giving the virus some advantage, or whether it is just by chance.
Viruses do not have a grand plan. 

They mutate constantly and while some changes will help a virus reproduce, some may hinder it. Others are simply neutral. They are a “by-product of the virus replicating,” says Dr Dorp. They “hitch-hike” on the virus without changing its behaviour.

The mutation that has emerged could have become very widespread just because it happened early in the outbreak and spread - something known as the “founder effect”. This is what Dr van Dorp and her team believe is the likely explanation for the mutation being so common. But this is increasingly controversial.

A growing number - perhaps the majority - of virologists now believe, as Dr Thushan de Silva, at the University of Sheffield, explains, there is enough data to say this version of the virus has a “selective advantage” - an evolutionary edge - over the earlier version. 

Though there is still not enough evidence to say “it is more transmissible” in people, he says, he is sure it is “not neutral”.
More dangerous?
When studied in laboratory conditions, the mutated virus was better at entering human cells than those without the variation, say professors Hyeryun Choe and Michael Farzan, at Scripps University in Florida. Changes to the spike protein the virus uses to latch on to human cells seem to allow it to “stick together better and function more efficiently”.

Two studies have suggested patients with this mutated virus have larger amounts of the virus in their swab samples. That might suggest they were more infectious to others. They did not find evidence that those people became sicker or stayed in hospital for longer, though.

In general, being more transmissible does not mean a virus is more lethal - in fact the opposite is often true. There is no evidence this coronavirus has mutated to make patients more or less sick.

But even when it comes to transmissibility, viral load is only an indication of how well the virus is spreading within a single person. It does not necessarily explain how good it is at infecting others. 

When it comes to looking at the population as a whole, it is difficult to observe the virus becoming more (or less) infectious. Its course has been drastically altered by interventions, including lockdowns.

But Prof Korber says the fact the variant now appears to be dominant everywhere, including in China, indicates it may have become better at spreading between people than the original version. Whenever the two versions were in circulation at the same time, the new variant took over. 

In fact, the D614G variant is so dominant, it is now the pandemic. And it has been for some time - perhaps even since the start of the epidemic in places such as the UK and the east coast of the US. So, while evidence is mounting that this mutation is not neutral, it doesn’t necessarily change how we should think about the virus and its spread.

bbc