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A new coronavirus variant is thought to have emerged in India.
Since the outbreak was identified on 31 December 2019, more than 3 million people are known to have died with the infection.
The roll-out of long-awaited vaccines offers hope for the future – however, the identification of new variants in Kent, South Africa and now India raises fears that the virus may no longer respond to the UK's three approved jabs.
A new variant could also spread more easily, evade natural immunity or even cause more severe disease.
Coronavirus cases are mounting in India, exceeding 17 million since the outbreak began – second only to the US.
The newfound variant is not necessarily responsible for India's huge, ongoing second wave. Nevertheless, many were alarmed when the variant was detected in the UK on 22 February 2021, followed by at least 103 cases.
While the variant is thought to make up 1% or less of the UK's total coronavirus incidences, evidence of community transmission prompted the government to put India on the travel red list.
Where has the variant been reported?
The variant – known as B.1.617 – was first submitted to the global database GISAID on 5 October 2020.
By 19 April 2021, B.1.617 had been picked up in 21 countries, with the US reporting its first case on 23 February.
Perhaps unsurprisingly, India has reported the most B.1.617 incidences. A lack of widespread testing means it is unclear if B.1.617 is the country's dominant coronavirus variant or driving its second wave.
Large gatherings at state-level elections, international cricket matches and religious festivals like Kumbh Mela may have become "super-spreading" events.
A lack of mask-wearing or inadequate hand washing could equally be to blame.
"Clearly this variant has increased in frequency in India around the time of their very large and tragic recent wave, but I don't think we yet know how much B.1.617 is driving that spread, versus its spread coincidentally happening at the same time," said Dr Jeffrey Barrett, from the Wellcome Sanger Institute.
"We did see some sequences of this B.1.617 variant late last year, so if it is driving the wave in India it has taken several months to get to this point, which would suggest it's probably less transmissible than the Kent B.1.1.7 variant."
Research has suggested B.1.1.7 spreads up to 70% more easily than earlier coronavirus variants.
Differences in how countries track variants means it is unclear exactly where B.1.617 is taking hold.
"The relative frequency of genomes from different countries is biased, because of the different amounts of sequencing being performed in different countries," said Professor Sharon Peacock, from the University of Cambridge.
"A country sequencing a high number of genomes may be more likely to detect variants."
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What makes the variant different?
The B.1.617 variant has been described as a "double mutant", due to the fact changes have occurred on its spike protein at positions called E484Q and L452R.
The coronavirus uses its spike protein to bind to a receptor present on many human cells, allowing it entry into the body. Many coronavirus vaccines target the spike protein, raising fears mutations will dampen – or worse, void – the jabs' effectiveness.
Overall, B.1.617 has 13 mutations that change the sequence of its amino acids; the building blocks of a protein.
Several of these have emerged in other coronavirus variants that also hit the headlines.
The E484Q mutation is "present in the three global variants of concern". According to Professor Peacock, "there is limited evidence for the role of E484Q in immune escape".
One experiment suggests variants with the E484Q mutation are less effectively "neutralised" by infection-fighting antibodies in people who have overcome the coronavirus naturally. This was not true in all cases, however.
The L452R mutation is also present in a variant that is thought to have emerged in California. This too "has been associated with weaker neutralisation of the virus" in coronavirus survivors.
How concerning is the variant?
In short, we do not know.
"When we see a new variant of the virus appear, there are generally four kinds of information we can use to evaluate it," said Dr Barrett.
"One of those is laboratory experiments, which we haven't had time to do yet on B.1.617, and another is real-world vaccine evidence, which takes even more time.
"The third source of information is to look at the specific mutations in a variant and to compare that to other variants that we know more about. The fourth is to see how fast it is spreading."
Ahead of further analysis, B.1.617 is listed as a "variant under investigation" by Public Health England.
It will only be classed as a "variant of concern" if evidence emerges of increased transmissibility, disease and immune escape, as well as reduced effectiveness of public health measures, like vaccination.
"This variant has a couple of potentially concerning mutations but these are probably not as serious as some of the mutations present in the variants first seen in Kent, South Africa and Brazil," said Dr Barrett.
"This could be because we have had less time to study them, so these mutations should be watched carefully."
When it comes to the E484Q and L452R mutations, Professor Ravi Gupta from the University of Cambridge said: "The worry is the two may have additive effects in making the virus less sensitive to antibodies. This is just a possibility at this stage, we don't have confirmation of it yet."
The variant also has a mutation at the site P681R, which could "enhance the amount of processed spike protein on the virus".
Based on laboratory experiments, this may then "impact the ability of B.1.617 to infect cells and possibly transmit," said Professor Gupta. "Again this is just a hypothesis at this stage, we don't know yet."
While India's critical situation may paint B.1.617 in a particularly bad light, experts have stressed the driver of its second wave is unclear and likely to be multi-faceted.
India is reportedly the world's biggest producer of vaccines, however, less than one in 10 (around 9%) of its residents are said to have been immunised.
"The disease is exposing the weak healthcare system," said Professor Martin Hibberd, from the London School of Hygiene & Tropical Medicine.
What's more, out of a population of around 117 million, just 17 million have been reported as having a natural coronavirus infection. Dr Julian Tang from the University of Leicester called this a "likely gross underestimate", however.
Nevertheless, he added: "Let's say the overall level of combined vaccine and natural immunity in India is about 10% – or about 140 million people – which still leaves the vast majority, 90% of the population, susceptible to the virus.
"I'm not sure how much the variants are contributing to this overall."
There is no evidence B.1.617 causes more severe disease or voids the effectiveness of coronavirus vaccines, however, any mutations are expected to dampen the jabs' action somewhat.
Like with seasonal flu, booster vaccines may be required to account for emerging variants.
In the meantime, experts are confident the UK's three jabs – Pfizer-BioNTech, University of Oxford-AstraZeneca and Moderna – still protect against severe disease and urge people to get immunised when called up.
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Are variants normal?
The fact the coronavirus is mutating comes as no surprise to experts.
The coronavirus is an RNA virus, which mutate relatively regularly. In simple terms, RNA is a precursor to the more well known DNA.
Most mutations are neutral, while others can be advantageous or detrimental to the virus.
Neutral and advantageous mutations can become more common as they pass to descendant viruses. Detrimental mutations tend not to "stick"; think survival of the fittest.
Some have pointed out it is unlikely to be a coincidence that new variants are emerging in countries with the most thorough viral genetic sequencing programmes.
Speaking of B.1.617, Dr Michael Head from the University of Southampton concluded: "There is still a lot to learn about this variant, such as whether it is more transmissible and thus contributing to an increased community transmission [in India].
"It is a plausible theory, but as yet unknown."