Mutant alert: Understanding the Covid UK variant and what it means for you

The new variant came to light in early December because of the UK's phenomenal genomic surveillance system for Covid-19. After looking at genomic analysis and epidemiological evidence of increased transmission, the Public Health England (PHE) concluded that "the new variant was showing signs of increased transmissibility."

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File photo: This scanning electron microscope image shows SARS-CoV-2 (round blue objects), also known as novel coronavirus, the virus that causes Covid-19. (Source: Reuters)

Last week, a new SARS-CoV-2 variant was identified in parts of London and southeast England where Covid-19 cases were surging. According to the Covid-19 Genomics UK Consortium (COG-UK Consortium) that sequenced the genome data of the virus and identified it, the new variant has been spreading "rapidly" over the last four weeks and has now been detected in other parts of the United Kingdom.

UK Prime Minister Boris Johnson recently said the new variant of SARS-CoV-2 could be up to 70 per cent more transmissible than other variants. This prompted several countries to impose limited or complete travel bans for the UK.

The new variant came to light in early December because of the UK's phenomenal genomic surveillance system for Covid-19. After looking at genomic analysis and epidemiological evidence of increased transmission, the Public Health England (PHE) concluded that "the new variant was showing signs of increased transmissibility."

The European Centre for Disease Prevention and Control (CDC), World Health Organisation (WHO), the US CDC, and the Public Health England technical briefing all clarify that current evidence only supports increased transmissibility and there is no evidence about increased or decreased disease severity, impact on reinfections, therapeutics or vaccines.

EXPLAINING THE BASIS OF MUTATION

Imagine SARS-CoV-2 as a tiny bubble with tiny clubs projecting out from its surface. The virus comprises different types of proteins and genetic code called RNA (ribonucleic acid) enveloped by a layer of fat (lipids from the bubble). The tiny clubs are called S proteins (spike protein) and they're a very important part of the virus. The S protein attaches to a specific receptor on host cells (called ACE-2), and if the fit is right, the virus can infect the cells. If the S protein is a partial fit, the virus may not be able to infect the cells as easily. The better the fit between the S protein and the receptor, the better the virus can infect the host cell.

The RNA genetic code consists of a series of letters and this represents the genetic blueprint to make all the coronavirus's proteins, including the S protein. The RNA blueprint determines which protein building blocks are present. These building blocks are called amino acids. A change in the virus's RNA may cause a change in its amino acids which can result in a change in the S protein.

When the virus infects a host cell, it tricks the host cell into making copies of viral RNA and proteins in a process called replication. During replication inside host cells, viral RNA needs to be copied thousands of times to make RNA for offspring viruses. During this process, a few errors may occur resulting in a different RNA genetic code. These errors are called mutations and the coronavirus mutates regularly, acquiring about one new mutation in its genome every two weeks.

Many mutations do not result in any changes in the amino acids that make proteins. Some mutations do result in a change in the amino acids but often have no functional impact on the virus's proteins. Occasionally, a mutation may occur that results in a change in a protein's function. For example, a mutation may result in a new amino acid that makes a new S protein which may fit better with the host cell ACE-2 receptor. This may create a virus that can infect cells better and pass more easily from one host to another.

Changes in proteins may also result in a longer duration of infection or a more severe infection. The opposite is also true; some mutations may result in a virus that is less transmissible and causes less severe infection.

Changes in the S protein can also impact immunity against the virus. Our immune response against the virus targets the S protein. If the coronavirus has a new S protein, then it may be able to escape an immune response against the old S protein. A coronavirus with a different S protein might cause reinfections in people who have recovered from Covid-19 and vaccines targeting the old S protein might become less effective.

When a set of specific mutations occur together, it can result in a new variant of the same coronavirus. Sometimes, a variant may have many mutations and some of these mutations may give the virus a functional advantage.

THE UK VARIANT

In early December, scientists in the United Kingdom studying Covid-19 observed a sudden spike in cases in parts of the country. They got concerned when genomic analysis revealed a new SARS-CoV-2 variant with many mutations occurring together. Concern caused alarm when they realised that over half of the new cases in that area were caused by the new variant. This variant has been named SARS-CoV-2 VOC 202012/01 (the first 'Variant of Concern' in December 2020) and is also called B.1.1.7.

The names VOC 202012/01, B.1.1.7 and UK variant are used interchangeably in the media and refer to the same SARS-CoV-2 variant. The UK variant is characterised by 23 mutations, an unusually large number of mutations, and several of these mutations have resulted in changes in the S protein.

Scientists are particularly concerned about mutations changing the amino acids in the spike protein in a way that changes the S protein's function. N501Y (a change at position 501 of the spike protein) and Spike deletion 69/70del (a double deletion at position 69 and 70 of the spike protein) are thought to increase transmissibility and impact molecular tests for Covid-19; studies are underway to determine if there's any impact on immunity.

PROBABLE IMPLICATIONS OF THESE MUTATIONS

Ability to spread more easily or quickly between humans:

These mutations have caused small changes in the S protein and it is thought this has resulted in a variant that is more transmissible.

While there is some uncertainty about the exact increase in transmissibility, experts at the Public Health England are confident that there is a significant increase in the variant's capability to pass on from one person to another. This is worrying because a more transmissible variant may cause many new Covid-19 infections, more hospitalisations and deaths.

Ability to cause milder or more severe infections:

Currently, there is no conclusive evidence that the UK variant causes more severe infections or has a higher fatality rate but there is also no evidence that it does not do so. More evidence is needed to make any claims about the impact on severity. Most healthcare systems across the world are already at peak capacity and any sudden spike in new cases would be a matter of serious concern.

Ability to evade immunity (reinfections and vaccines):

The S protein enables the coronavirus to infect host cells and therefore, natural immunity following Covid-19 and vaccines both target this S protein.

The S protein is an antigen, which is a protein that triggers an immune response. Antigens have different parts that the immune system can recognise; these are called epitopes or antigenic determinants. A mutation may change just one antigenic determinant on the S protein but there are many others that are still the same and therefore, the immune system can still recognise the S protein. The immunity developed following recovery from Covid-19 or after complete vaccination targets multiple antigenic determinants on the S protein, so even if one part of the S protein changes, there will still be some protection against the new variant.

Currently, there is no evidence that those who have recovered from Covid-19 in the past are at increased risk of reinfections due to this new variant. The Menachery Lab tweeted out data that suggests patients who have recovered from Covid-19 in the past have antibodies that may protect against variants with N501Y.

While this is good news, this data has not been peer-reviewed outside of Twitter and the UK variant has other spike mutations that could have some impact on reinfections. Again, more evidence is needed to make any claims about reinfections.

Everyone should be reassured that existing vaccines target the entire S protein and early evidence indicated post-vaccination immunity is robust. So, we have reasons to expect that existing Covid-19 vaccines will offer protection against the UK variant. The possibility of a modest decrease in the efficacy of Covid-19 vaccines is something that is being investigated vigorously by scientists in the UK.

Some authorities have issued false reassurances that this variant is not causing more severe infections and that it will have no impact on vaccines. Others have caused alarm and panic by suggesting the UK variant is a super mutant virus. Both positions are entirely unsupported by available evidence.

THE ROAD AHEAD

In response to news of the UK variant, many countries, including India, have imposed travel restrictions. These are sensible first steps but it's likely that the new variant is already spreading undetected in India. Detecting new mutations requires advanced genetic tests and the UK is the world leader in this area of science.

The United Kingdom performs more such tests in a single month than most countries have performed in total since the pandemic started. The UK was looking for variants and it found one of concern. Other countries, India included, need to step up surveillance systems. The Indian Council of Medical Research has started looking for the variant in India.

We should be concerned about the more transmissible UK variant, but we should also be concerned about human behaviour that increases transmission. Each and everyone of us has a role to play in the battle against the virus.

(A Covid-19 clinical researcher, Dr Swapneil Parikh is author of The Coronavirus: What You Need to Know About the Global Pandemic)