December 14, 2020

expert reaction to the new variant of SARS-CoV-2

Matt Hancock announced that a new variant of SARS-CoV-2 has been identified in his speech to the House of Commons.

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The changes in the SARS-CoV-2 sequence are variants not strains.  The virus exists as a cloud of variants known as quasispecies and individual viruses are selected at the time of infection, much like lottery balls.  When the virus multiplies it regenerates extensive variation but retains a relatedness to the original infecting virus.  It is this relatedness that has been noted and given rise to the concern that a “new strain” is emerging.  In my view this is unlikely for several reasons.  First, a new strain cannot come to predominate unless it provides some advantage to the virus and none has so far been reported.  Second, an adventitious variant is most likely to arise in the parts of the world where infection is rampant, not the UK.  Third, the previous reports of emerging variants, D614G, N439K and the “mink” virus have not translated into a new “strain” so it is unlikely the SE England variant will behave differently.  Virus tracking is important but the reassuring conclusion so far is that the variation observed is largely “noise in the machine” which, as the vaccine protection data has shown, does not mean that current approaches to prevention need to be modified.”

Dr Lucy van Dorp, senior research fellow in microbial genomics at the UCL Genetics Institute, said:

“It is frustrating to have claims like this made without the associated evidence presented for scientific assessment and the variant remains to be officially announced. It seems COG-UK will release further details soon¹ and a preprint may follow².

“The possible candidates based on some of our own observations (current as of 30^th November) is that this may refer to a double deletion in the coronavirus spike protein (positions 69/70) or alternatively a spike mutation in the receptor binding domain N501Y³. There is some experimental support for N501Y increasing receptor binding experimental settings and mouse models. There have also been some reports that the spike double deletion has a moderate impact on antibody recognition.

“At the same time it is important to remember that all SARS-CoV-2 in circulation are extremely genetically similar to one another and our prior should be that most mutations have no significant impact on the transmissibility of SARS-CoV-2. However genomic monitoring is essential to allow us to stay one step ahead.”

¹ https://twitter.com/alanmcn1/status/1338529352959619075

² https://twitter.com/GuptaR_lab/status/1338541743667630088

³ https://twitter.com/firefoxx66/status/1338533710178775047

Dr Simon Clarke, Associate Professor of Cellular Microbiology at the University of Reading, said:

“Health Secretary Matt Hancock has linked the discovery of a mutation in the virus’ spike protein to increased transmission; while that is yet to be verified, it would be of grave concern if it indeed proves to be the case. While Hancock states that there is “nothing to suggest” this variant will cause more serious disease, if it spreads more readily than other versions, infecting more people, it could eventually take a bigger toll on human health.”

Dr Zania Stamataki, Viral Immunologist, University of Birmingham, said:

“The emergence of different coronavirus strains a year after SARS-CoV-2 first jumped to humans is neither cause for panic nor unexpected. Mutations will accumulate and lead to new virus variants, pushed by our own immune system to change or perish.

“This virus doesn’t mutate as fast as influenza and, although we need to keep it under surveillance, it will not be a major undertaking to update the new vaccines when necessary in the future. This year has seen significant advances take place, to build the infrastructure for us to keep up with this coronavirus.”

Prof Tom Solomon, the Director of the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, at the University of Liverpool, said:

“SARS-CoV-2, the virus which cause Covid-19 is evolving and mutating all the time, as do all similar viruses. Such changes are completely to be expected.

“In the UK we are doing very detailed genetic assessment of many of the virus strains detected. From what Matt Hancock has announced it sounds as though a particular variant is being detected especially across the South of England. Just because there has been a small change in the virus’ genetic make-up this does not mean it is any more virulent, nor that vaccines won’t be effective.  Our experience from previous similar viruses suggests that the vaccines will be effective despite small genetic changes.”

Prof Julian Hiscox, Chair in Infection and Global Health, University of Liverpool, said:

Is this to be expected?

“Yes, this has been known for many years with coronaviruses.  Coronaviruses have two mechanisms of mutation.  If we look at animal coronaviruses, such as infectious bronchitis virus of poultry, there are hundreds of different variants of that virus.  There are many different variants of the different seasonal human coronaviruses, and with those people can become reinfected within six months to a year.

Are new variants always more virulent?

“No, not always, but in feline (cat) coronaviruses, within host change in a single infection can lead to a new more virulent virus being formed.  In other coronaviruses, some have ‘changed’ that have become less virulent e.g. pig coronaviruses.

Is this a big deal?  Should we be alarmed?  How should it change our response, if at all?

“We should be cautious and focus efforts on understanding the transmission of this virus and if necessary introducing control measures to prevent its spread.  There is always a lag between sampling and information.  Currently there is no evidence that this virus will evade the vaccine or will lead to increased disease or death.

What will PHE be doing to analyse it?  What do we need to know about it?

“PHE will be focusing on sequencing the virus from patients to determine its prevalence in the population and conducting analysis of the biology of the virus e.g. does it grow more quickly or the same as other strains.  They will also be checking that the nucleic acid based diagnostic remain fit for purpose as many of these target the spike gene.  This illustrates why we need a rapid mechanism in the UK to understand these so called genotype to phenotype changes.

Why should we be confident that it will still respond to the vaccines? 

“We know from other coronaviruses that small changes in the spike glycoprotein (that is the target of the vaccine) can lead to vaccine escape.  We have no evidence at the moment whether this variant will or won’t respond to the vaccine.  This illustrates that we need to be agile and flexible with the vaccine platforms and will probably be like seasonal influenza viruses where we have to give multiple vaccines that change with time.

How different do variants need to be for one to resist a vaccine?

“This depends on where the variants are located in the vaccine target.  If this is in what is called the receptor binding domain of spike then variants may be refractive to the vaccine.  This illustrates why for most animal coronaviruses the vaccines are multi-valiant i.e. target a number of different viral proteins.”

Prof Richard Tedder, Senior Research Investigator in Medical Virology, Imperial College London, said:

“In reality, when one has a species jump of a virus, it is not at all surprising if the virus undergoes a period of adaptation to the new host. This does not necessarily bring about a change in the degree to which the virus causes disease; in fact some of the most effective agents at establishing themselves in the human population recently have exploited long periods of apparent clinical harmony with their new host, HIV being a case in point. So, although the initial primary host of SARS-CoV-2 may not be known with absolute certainty, on the scale that we now see this is clearly a new infection in our species. One has seen a natural evolution of genetic variants for example in HIV, a recent human acquisition. One also sees well documented existence of variants in hepatitis B, a virus in humans of great antiquity, which comprise a number of sub families, better described as genomic variants, or genotypes, which after millennia are stable and circulate as stable variants throughout the human population.

“Viral variation is “normal”. Whilst it is important to keep a genetic eye on the current coronavirus, variation is bound to occur as the numbers of infections and transmissions increase in what is a relatively early stage of this human-virus relationship. This becomes of critical importance if any established variation confers the virus a biological advantage over the host – and the advantage can take many forms. At present, science needs to document genetic variants as we learn more about the diversity of the host-virus relationship and keep a watching brief for evidence of viruses with altered behaviour.”

Prof Martin Hibberd, Professor of Emerging Infectious Disease, London School of Hygiene & Tropical Medicine (LSHTM), said:

“Reports of a new variant of the SARS-CoV-2 virus in the south of England is not surprising and it is too early to say how important it is yet.  

“It is truly a wonderful worldwide effort that is ensuring that changes in the virus are being monitored, and the UK has been an important part of that. As the vaccines are introduced, this will become a more important process, to ensure that any vaccine escape mutants that could theoretically develop are quickly identified and isolated. In the nearly a year since the first sequencing of SARS-CoV-2, many genetic variants have been identified. These have been useful in understanding the worldwide spread and transmission pattens, but scientists think that only one of these has previously conferred an advantage to the virus. That advantage did not make the virus more virulent, and should not affect vaccines or treatments, but did seem to make the virus slightly more easily spread from one person to the next. This has meant that strain is now the most common variant seen in many parts of the world.

“The newly observed variant in England may be similarly important and perhaps offer an advantage to the virus by becoming more transmissible, but the observation may also be the result of chance events. We are fortunate that we are able to monitor and evaluate this and will no doubt be able to calculate a thorough analysis from the evidence soon.”

Dr Stephen Griffin, Chair of the Virus Division at the Microbiology Society, and Associate Professor in the School of Medicine at the University of Leeds, said:

“Even though Coronaviruses tend to mutate more slowly than some other viruses, this does not mean that they won’t change over time. It is encouraging that our surveillance systems have picked this variant up, but it is important that we understand how this change in the virus spike protein might affect the behaviour of the virus. Importantly, laboratory experiments will be needed to understand how this genetic change may, or may not be linked to the increases in cases in the UK and elsewhere. Importantly, this change is unlikely to affect the efficacy of vaccines, but it remains to be seen whether it causes an effect on how easily the virus spreads from person to person.”

Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, said:

“The emergence of new genetic variants is a natural process that viruses undergo during protracted epidemics. Invariably the mutations responsible for the new genetic variants are neutral and have little effect on the transmission and virulence of the virus.

“It is impressive that this new variant has been picked up so quickly by the COG-UK genomics teams and this should allow us to monitor and study in detail this emergent variant to ascertain if it could potentially be more problematic.”

Prof Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“Genetic variants arise relatively frequently in viruses as a result of errors in copying viral genetic material. These can lead to small changes in virus proteins.

“Such changes may improve virus replication and make SARS-CoV-2 grow a little faster. Such a genetic variant may outgrow other viruses in an individual, and is thus more likely to spread to other people. In a short time, a virus carrying such a genetic change will predominate in the population.

“There are several precedents for SARS-CoV-2 viruses arising with enhanced growth properties but no evidence that any of them cause worse disease. However, viruses with altered genomes may also increase in number simply because they arose in someone who happens to infect a lot of other people, perhaps in a crowded gathering, rather than because the virus has changed properties.

“Experiments with purified viruses to test whether observed genetic changes result in altered properties of the virus will be needed to distinguish between these possibilities.  Use of such virological analyses is a vital tool for the further monitoring of potential virus evolution as the COVID-19 pandemic unfolds.”

Dr Jeremy Farrar, Director of Wellcome, said:   

“While research is ongoing, there is evidence to indicate a new variant of the Covid-19 virus. There have been many mutations in the virus since it emerged in 2019. This is to be expected, SARS-CoV-2 is an RNA virus and these viruses mutate and change. The pressure on the virus to evolve is increased by the fact that so many millions of people have now been infected. Most of the mutations will not be significant or cause for concern, but some may give the virus an evolutionary advantage which may lead to higher transmission or mean it is more harmful.   

“The full significance of this is not yet clear – that includes whether a new strain is responsible for the current rise of infections in parts of the UK and, if so, what this may or may not mean for transmission and the efficacy of the first vaccines and treatments. This is potentially serious; the surveillance and research must continue and we must take the necessary steps to stay ahead of the virus. 

“Above all, this is a reminder that there is still so much to learn about Covid-19. The pace of the research effort in the past year has been extraordinary, allowing us to make significant progress on the vaccines, treatments and diagnostics needed to end this crisis. The speed at which this has been picked up on is also testament to this phenomenal research effort. However, there is no room for complacency. We have to remain humble and be prepared to adapt and respond to new and continued challenges as we move into 2021. This pandemic is not over and there will still be surprises in the virus, how it evolves and the trajectory of the pandemic in the coming year. 

“2020 has been a tough year; tough beyond belief for millions across the country, and across the world. Unfortunately, more difficult months lie ahead and the consequences of relaxing our focus or not having sufficient restrictions will result in more suffering.  We have to respect the restrictions and accept that there will be a need for these to be tightened when infection rates rise, or as new information is learned about this virus.” 

Dr Andrew Davidson, Reader in Virology at the University of Bristol, said:

“When viruses like SARS-CoV-2 replicate they are constantly mutating. However only changes that make them more “fit” for transmission are likely to be stable and result in new circulating strains. This does not mean that a new virus will cause more severe disease or avoid vaccines but it could transmit more efficiently between people. This has already happened for SARS-CoV-2. A change in the viral spike (termed the D614G change) is believed to have increased the ability of viruses with this change to be transmitted and this strain is now dominant in many countries. A number of studies suggest however, that the new strain does not result in more severe disease. It is very important that we carry out active surveillance to identify changes in SARS-CoV-2, as they occur, and study the properties of any new viruses to determine if they pose a greater threat to human health. Preparedness is key to prevention of spread and updating vaccines if necessary.”

Is this to be expected? 

“Yes, coronaviruses are known to mutate.”

Is it the first of its kind detected in the UK?

“A number of variants have been detected using sequencing studies in the UK. A specific variant (the D614G variant) has previously been detected in Western Europe, Nth America etc which is believed to spread more easily but not cause greater illness.”

Are new variants always more virulent?

“No they could even be less virulent. However if they spread more easily but cause the same disease severity more people will end up becoming ill in a shorter period of time.”

Is there any reason to expect it to be more or less harmful?

“No – the main selection is for the virus to spread, it would only become more harmful if this also helps spread.”

Is this a big deal?  Should we be alarmed?  How should it change our response, if at all?

“Hard to say at this stage. However a virus that spreads more easily will hamper control efforts.”

What will PHE be doing to analyse it?  What do we need to know about it?

“Sequencing virus isolates that emerge and trying to determine if it is spreading more rapidly than existing isolates and outcompeting them.”

Why should we be confident that it will still respond to the vaccines? 

“The vaccine produces antibodies against many regions in the spike protein it is very unlikely a single change would make the vaccine less effective. However this could happen over time as more mutations occur (happens every year with flu for example).”

Prof Wendy Barclay, Head of the Department of Infectious Disease, Imperial College London, said:

“SARS CoV2 is an RNA virus and mutations are expected to occur as it replicates.  It is essential that we understand the consequence of any changes in the genome of the virus – for example, how this might impact on disease, transmission and the immune response to the virus.

“Some variants with changes in the Spike protein have already been observed as the virus is intensely sequenced here in the UK and around the world.  There is no evidence that the newly-reported variant results in a more severe disease. This variant contains some mutations in Spike protein that is the major target of vaccines, and it will be important to establish whether they impact vaccine efficacy by performing experiments in the coming weeks.”

Prof Alan McNally, Professor in Microbial Evolutionary Genomics at the University of Birmingham, said:

“Over the past few weeks a few of the UK PCR testing labs have picked up on this new variant. Supported by The COVID-19 Genomics UK (COG-UK) consortium and rapid genomics it has been identified incredibly quickly.

“Hopefully the narrative here is how amazing our surveillance has been at picking this up. Huge efforts are ongoing at characterising the variant and understanding its emergence. It is important to keep a calm and rational perspective on the strain as this is normal virus evolution and we expect new variants to come and go and emerge over time. It’s too early to be worried or not by this new variant, but I am in awe of the surveillance efforts in the UK that allowed this to be picked up so fast.”

Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“The genetic information in many viruses can change very rapidly and sometimes these changes can benefit the virus – by allowing it to transmit more efficiently or to escape from vaccines or treatments – but many changes have no effect at all.

“Even though a new genetic variant of the virus has emerged and is spreading in many parts of the UK and across the world, this can happen purely by chance. Therefore, it is important that we study any genetic changes as they occur, to work out if they are affecting how the virus behaves, and until we have done that important work it is premature to make any claims about the potential impacts of virus mutation.”

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

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