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Source: United Kingdom – Science Media Centre

The Prime Minister and the Chief Medical Officer made a statement about new Tier 4 restrictions, the new SARS-CoV-2 variant and updated guidance over Christmas.

Dr Jeffrey Barrett, Director of the SARS-CoV-2 Genomics Initiative at the Wellcome Sanger Institute, said:

Comment in response to questions about the new variant and the PCR test:

“One of the mutations in the new variant deletes six bases in the viral genome that encode amino acids 69 and 70 of the spike protein.  By coincidence, this region is one of three genomic targets used by some PCR tests, and so in those tests that “channel” comes up negative on the new variant.  However, the other two channels, which are not affected by the new variant, provide redundancy, and mean that the virus is still detected by the combined test.  I’m not aware of any commercial tests that use just one target in this part of the viral genome, but if there are, they should be carefully investigated.”

Dr Robert Shorten, Chair, Microbiology Professional Committee, Association for Clinical Biochemistry & Laboratory Medicine (ACB):

Comment in response to questions about the new variant and the PCR test:

“Some of the PCR (swab) tests detect part of the spike protein gene that has recently been reported to have mutated.  This has affected the ability of some tests to detect the virus.  Laboratories know which genes their tests target and are vigilant about checking for test performance.  PCR tests would generally detect more than one gene target so a mutation in the spike protein would not affect detecting other viral gene targets, which mitigates the risk of reporting a false negative result.  All viruses mutate and vigilance and quality systems used by diagnostic laboratories is always important.”

Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:

“The new SARS2 variant may well be cause for significant concern, and all the more reason to be vigilant.  However, that it has taken an event of this nature to provoke a reaction from the government says more about the current scenario in the UK and the long term view of how this came to be, rather than the naturally upsetting and disappointing false promises over Christmas that have now been revoked.

“It is clear that failure to make good on the sacrifices made during the first lockdown, suppress infection rates over summer, and replace the failed corporate TTI system has led directly to the resurgence seen since September, the need for a second (and likely a third) lockdown, and ultimately an environment in which SARS-COV-2 is able to thrive and evolve.  Half-baked policies neither restore socio-economic harms, nor suppress infections, and the reactionary, fragmented and confusing implementation of Tiers along with their obscure criteria has led to public favour eroding day by day.  We are left at the mercy of misinformation and fringe viewpoints.

“Nevertheless, if it takes the new variant to finally convince our leaders to implement an effective suppression strategy along with the long-recommended safeguarding on TTI, quarantine and internal travel, then so be it.  We cannot simply stand by and wait for vaccines to rescue the situation, the human cost has already been far too high.”

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“The suggestion that the variant arose in a chronically infected individual is plausible but unless we have sequences from that individual it would be difficult to prove.

“It is known that viral variants are more likely to arise in people who are chronically infected, though the evidence for this primarily comes from those viruses that routinely cause chronic infections such as HIV and Hepatitis B.  Indeed in these infections the generation of what are known as immune escape mutants are an important part of how the virus may cause continuing disease.  We do know that in immunocompromised patients SARS-CoV-2 can shed COVID for quite a long time1, but so can immunocompetent patients2.  Also we do know that mutations in SARS-CoV-2 are more likely to occur in chronically infected immunosuppressed individuals as referred to in the paper by Rambaut and colleagues3.

“Nevertheless mutation in viruses are a random event and the longer someone is infected the more likely a random event is to occur.  So Rambaut and colleagues’ suggestion the this variant arose in a chronically infected individual is highly likely and that any person chronically shedding the virus is more likely to be immunosuppressed is also highly likely.  But, we may not be able to provide this for certain.”

1. Aydillo T, Gonzalez-Reiche AS, Aslam S, van de Guchte A, Khan Z, Obla A, Dutta J, van Bakel H, Aberg J, García-Sastre A, Shah G. Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer. New England Journal of Medicine. 2020 Dec 1.

2. McKie AM, Jones TP, Sykes C. Prolonged viral shedding in an immunocompetent patient with COVID-19. BMJ Case Reports CP. 2020 Oct 1;13(10):e237357.

3. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

Dr Jeffrey Barrett, Lead Covid-19 Statistical Geneticist, Wellcome Sanger Institute, said:

Regarding the number of mutations of the new variant:

“Our virological post1 lists the 17 non-synonymous, or coding, mutations.  These are ones that change the protein sequence of one of the viral genes.  There are also a couple of synonymous (sometimes called “silent”) mutations that don’t have any function, but crop up and come along for the ride.  So I think Patrick Vallance was counting the total number, whereas the biological investigations are really focused on just the coding changes.”

1 https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563

Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:

“The priority given to  genomic analysis of samples from Tier 4 regions may have changed in December 2020 to prioritize investigation of novel variants. This would be a cogent response to the current public health emergency but might mean that limited capacity for genomic analysis had to be re-assigned in non-Tier 4 regions. Hence, the following questions arise:

“1. What percentage of SARS-CoV-2 cases is subject to genomic analysis (Scotland’s press conference suggested 5% to 10%).

2. What is the typical lag between swab-date for SARS-CoV-2 positive cases & genomic analysis-date for samples sent for genomic analysis? (Scotland suggested weeks, not days).

3. What increase in sampling fraction was made for Tier 4 regions as concern mounted about the novel virus? (this would be scientifically-efficient).

4. What change, if any (including decrease), was made in sampling fraction outside of Tier 4 regions?

5. What acceleration in throughput of genomic analyses was made for Tier 4 regions as concern mounted about the novel virus? (this would be warranted scientifically & for public health).

6. What change, if any (including deceleration), was made in throughput of genomic analyses outside of Tier 4 regions?

7. Did No10 press conference slides refer always to swab-date?

8. If not, which dates are used on which slides?”

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“Regarding the N501Y mutation within the new B.1.1.7 lineage, part of the 20B/GR SARS-COV-2 clade, which was already defined in this earlier paper (Fig 1):

https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.32.2001410

“An examination of the global GISAID SARS-COV-2 sequence database shows that this N501Y mutation was actually circulating, sporadically, much earlier in the year outside the UK: in Australia in June-July, USA in July and in Brazil in April, 2020.”

“Whether or not these viruses were brought to the UK and Europe later by travellers or arose spontaneously in multiple locations around the world (in response to human host immune selection pressures) requires further investigation.”

Prof Peter Horby, Professor of Emerging Infectious Diseases, Centre for Tropical Medicine and Global Health, University of Oxford, said:

“The conclusion of increased transmissibility is based on various sources of converging data, including, but not limited to, the rate of change in the frequency of detection of the variant (the growth rate) and the correlation between R-values and the frequency of detection of the new variant.”

 

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

“Coronaviruses mutate all the time so it is not unexpected that new variants of SARS-CoV-2 are emerging, we see this all the time in other human and animal coronaviruses. We have great systems in place in the UK to identify these variants to inform a public health response. The most important thing is to investigate whether this variant has any new properties that impact on human health, diagnostics and vaccines. We need robust mechanisms in place to do this.

“The control measures are appropriate – better to be cautious. Stopping the spread of this virus is simple: people need to follow and obey the guidance of the Tier system and have common sense. The more people you come into contact with, the more chance of spreading. So avoid social mixing – it’s not long to wait for the widespread roll-out of the vaccine.”

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“Regardless of this new 501Y virus variant, from a purely virological/epidemiological viewpoint, the new restrictions over Christmas and the new Tier 4 for the hardest hit London/Southeast areas are a necessary measure to control this virus.

“But unfortunately, even mixing amongst 3 households (with as many as 10-15 people) in the other Tiers, over 6-8 hrs on Christmas Day, is more than enough to spread this virus – and it is likely that many more people are now going to do this, now that the opportunity is limited to just one day.

“So I would still urge people to restrict the duration and number of households mixing, open the windows (even just halfway) to protect the elderly – including asking them to maintain social distance as much as possible within the house, and to mask when not eating/drinking.

“If this new 501Y virus variant really is more transmissible, then even brief exposures may still result in infection.”

 

Dr Shaun Fitzgerald, Royal Academy of Engineering Visiting Professor at the University of Cambridge, said:

“The situation at present is extremely concerning and we are on a precipice. That’s why hard decisions about Christmas have to be made. If households do mix on Christmas Day, there is even more reason to be absolutely fastidious about the measures we can all take to help reduce the risk of transmission.

“We know how this horrible virus spreads, and we all need to disrupt the pathways. Hands, face, space, ventilation – and limit our social interactions. 3 households is a maximum, not a target. Just like speed limits – it’s safer to go below them.”

Prof Peter Openshaw, past-President of the British Society for Immunology and Professor of Experimental Medicine at Imperial College London, said:

“The information that the government has just issued about this new variant coronavirus is of great concern. It is right to take it seriously; although there are only 23 mutations in the genetic code of 30,000 nucleotides the variant does seem about 40-70% more transmissible. The doubling time is now at just 6 or 7 days so it is really vital that we get this under control.  

“The spread of this new variant has been associated with an increase in hospitalization, especially in Kent and London; however, there is no evidence at the moment that the new variant causes disease which is any different from that caused by previous variants.

“It is a tribute to the genomic surveillance by COG-UK that the variant has been detected so quickly. The reasons for the enhanced infectivity are not yet clear. We need to know if it is due to more viral replication or better binding to the cells that line the nose and lung. There is currently no direct evidence that the virus is able to evade immunity generated by past infection or by vaccination, but there is good reason to think it won’t. All this needs to be investigated.

“It is also remarkable that 350,000 people have already received the first dose of the Pfizer/BioNTech Vaccine. It is vital that vaccination is ramped up as fast as possible to control the effects of infection on the most vulnerable, and to get front-line workers protected. I absolutely urge everyone being offered vaccination to get vaccinated.

“This holiday period is important to all of us and we are all devastated to hear this news.  However, now is the time to reunite in the fight against the virus rather than arguing between ourselves. Let’s enjoy Christmas as best we can, and celebrate again in the spring and summer when we hope all this will be over.”

Dr Jeremy Farrar, Director of Wellcome, said:  

“The new strain of Covid-19 is highly concerning and it is right to act with urgency as the government has done. The changes announced deserve all our support. 

“Research is ongoing to understand more, but the infection rate is clearly rising very rapidly, particularly in London and the south-east of England. The data shows the new strain is more transmissible and has led to more infections and a worrying increase in the r-rate.  

“At the moment, there is no indication that this new strain would evade treatments and vaccines. However, the mutation is a reminder of the power of the virus to adapt, and that cannot be ruled out in the future. Acting urgently to reduce transmission is critical. 

“Difficult as this year has already been, we must stay humble. There are still many unknowns about Covid-19 and it remains a grave threat to us all.  

“There is no part of the UK and no country globally that should not be concerned. As in the UK, in many countries the situation is very fragile.  

“It may feel harder during times we normally celebrate and enjoy with family and friends, but we must keep doing all we can to stay safe.  

“We will only end this pandemic with a combination of vaccines, tests and treatments, available to everyone, everywhere. The pace of global research has been phenomenal and we have made significant progress on the tools needed. However, we must be realistic; this pandemic is not over and it will take some time for the first vaccines to have the impact needed.  

“Through 2020 much of this pandemic has been predictable, waves of infection reverberating globally as behaviour changes and restrictions are relaxed. We may now be entering a less predictable phase as the virus evolves and changes. 

“We must keep asking ourselves ‘are we doing enough’ and responding fast to new and continued challenges, in order to save lives now and as we move into 2021. 

“Only tighter restrictions can curb infection rate rises and we have to reduce transmission to prevent hospitalisations and deaths. We must pay tribute to healthcare workers and global research community everywhere, working tirelessly on behalf of all of us. We owe them all our thanks and support and to be willing to take every precaution.” 

 

 Dr James Gill, Honorary Clinical Lecturer, Warwick Medical School, said:

“Hearing that the Tier 4 restrictions have been initiated in the south of the country is obviously going to be a shock and a disappointment. In the early stages of the COVID19 outbreak, criticism was directed at the slow pace of response and distinct action which will have been a contributing factor to the degree of COVID19 spread over the past year. 

“Viruses change, there have been observed changes previously in COVID19 and countries have been affected by different strains, but crucially these strains have not resulted in any relevant clinical changes such as new symptoms. We have been able to detect and act on this new variant due to exceptional work going on in labs across the country that have been tasked to monitor the genetic code of the COVID19 virus – specifically watching for this eventuality, the rise of a new variant.  With the latest variant, we are seeing an increase in infectivity, and it appears this latest COVID19 strain is one of the main driving factors in the rise in cases in the South. Thus it is correct, prudent and sensible to act now as we learn more.

“We are still waiting to learn further about this new strain, and that has to be the key information here, it appears to be more contagious but we do not know if it is more or less dangerous. Hence the stronger restrictions are sensible. The greater curbs on social interactions – even at Christmas – allow time for scientists to learn and characterise this new strain, and in doing so, prevent the repeat of mistakes that were made in the earlier stages of the pandemic. 

“Being reactive with a virus is very difficult.  Whilst an over-used phrase, it is shutting the door after the horse has bolted. In this current situation being proactive, taking very strong steps, is the right thing to do. To be very clear, delaying introduction of new restrictions whilst we gather further data on this new strain will cost lives. When scientists have a clearer picture of the clinical relevant changes that are present in this strain, we will be able to safely review our restrictions. 

“Science and medicine is driven by data. To act without being guided by data is foolish at best, dangerous at worst. Currently the data are suggesting a rise in new infections as a result of this new strain, so it is sensible to instigate restrictions to gather new data.”

 

Prof John Edmunds, Professor in the Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, said:

“There are 3 key questions that need to be addressed when a new strain emerges: is it more pathogenic? Is it different enough to evade the immune response generated by previous infection or vaccination? And is it transmissible?

“At present we have no information on the first two questions, but over the last few days we have begun to get an answer for the third and the answer is very bad news. It looks like this virus is significantly more infectious than the previous strains. This means that to control it we are going to have to put in place much more restrictive measures. I am sorry to say that it looks like there are tough times ahead, but the faster and more decisively we act the quicker we can begin to control this new virus.”

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

“I’m not certain that I understand the rationale of a partial imposition of Tier 4 rules.  If enhanced restrictions are required to control the spread of the variant, why aren’t they being imposed across the whole country?  If the variant virus arose only once and, because of a genuine increase in enhanced transmissibility, spread to the 50% we see in the Southeast under Tier 3 rules, how can we be confident that in the next few weeks the reported 5% incidence in other parts of the country will not rise to 50%? Better to act sooner than later!”

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“Today’s press briefing was perhaps not too surprising. We did hear more information about this new variant SARS-CoV-2 virus. We were told by Sir Patrick the following important points

  • There has been very dramatic increase in cases and hospitalisations in London and the South East relative to the rest of England in the past days and this increase does seem to be caused by the new variant.
  • The new variant is not just due to a single mutation and there are some 23 different mutations many of which are associated with the Spike protein that the virus used to get into cells.
  • The variant is thought to have occurred sometime in September in London or Kent.
  • That the virus variant is substantially more infectious is clear from the fact that in early November it was responsible for 28% of infections in London and in the week ending 9th December it was responsible for 62%.  The PM said that early analyses suggest that the new variant seem to be 70% more infectious and to have increased the R value by 0.4 or more.
  • Currently there’s no evidence it causes more severe disease. At present the current vaccine should still be effective.
  • There is also some suggestion that the new variant is spreading elsewhere. Indeed, if you look at the Dashboard data for the South West, East Midlands and West Midlands it does look like cases are starting to increase there as well.  

“That viruses mutate to become more infectious is not surprising and that this could happen with new and emergent viruses has been known for some time.

“To me these reports on the transmissibility of the new variant are even more depressing than I had anticipated. An increase in R of 0.4 or greater is extremely bad news. During the national lockdown in November the best we could achieve was an R value of somewhere between 0.8 and 1.0 around the UK. What this means is that even if we went back to the National Lockdown it would still not be enough to bring the R value down to less than 1.0. It is even uncertain whether if we went back to the lockdown of March and April we would bring the R value down to less than 1.0. So, perhaps, all we can now hope for is that the epidemic increases less rapidly with the measures that the PM announced today.  

“Although the vaccines should still be as effective as reducing the risk of severe disease in death in people vaccinated. The increased transmissibility reported today does mean that even with some benefit from vaccine on reducing transmissibility, the vaccination programme is even less likely to protect those people who choose not to be vaccinated.

“It is inevitable that this new variant will spread throughout the UK and we can expect to see increased transmission rates in all regions and devolved administrations over coming weeks. As yet I know of no evidence that the new variant has spread overseas but I suspect that this is only a matter of time and we will see similar problems in other countries from this new variant.

“The appearance of such an infectious variant of the virus at this time of year represents a perfect storm for the epidemic and is desperately bad news for attempts to control the epidemic.”

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“The escalating case numbers mean that dramatic interventions are essential, so the new announcements are important and will help to provide some element of control on the national landscape. However, it has been obvious for some time that mixing of multiple households over the Christmas period will lead to a very difficult January. Therefore, this level of restrictions is what should have been implemented at the time of the previous Christmas announcements, regardless of the impact of this new variant.

“There are several other countries that have strong measures in place over Christmas, and there is plenty of precedent where large public festivals that have been cancelled or curtailed due to COVID-19, such as the Hajj in Saudi Arabia being scaled right back, and a ban on household mixing during Passover in Israel.”

Dr Jeffrey Barrett, Director of the Covid Genomics Initiative at the Wellcome Sanger Institute, said:

“This new variant is very concerning, and is unlike anything we have seen so far in the pandemic. The new restrictions announced today are an entirely justified response to the rapidly developing situation. Detecting new variants like this is one of the key missions of the Covid-19 Genomics Consortium in the UK. The high level of genomic surveillance we have had to date has helped detect and respond to this variant as quickly as possible. We will continue to monitor this and other variants in the weeks and months to come.”

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

“Viruses mutate constantly. The coronavirus has mutated many times over the last year.  This helps scientists to track how infections are spreading. For example, we know that most of the infections in the UK in the first wave came not directly from China but from Europe, where a new variant emerged that was different from the strain in Wuhan.

“Government scientists have identified now that there are 17 linked mutations in the genetic code of the virus that seem to make this new strain more infectious. It has been suggested that changes to the virus surface spikes may allow it to bind onto cells more easily.  However there isn’t evidence yet that the new virus is more or less dangerous in terms of its ability to cause disease.  Sadly, we will have to wait and see if hospitalisations and deaths increase or decrease to find out.”

 

Prof Daniel Altmann, Professor of Immunology, Imperial College London, said:

“From the graphics as presented, this variant sequence has certainly become more prevalent in the southeast, correlating with an upturn in caseload.  As far as I can see this greatly strengthens the case for all to get vaccinated as soon as possible: the vaccines induce neutralising antibodies to several parts of spike (‘epitopes’) and most of these would be unchanged by the mutations – so the vaccines will still work.”

Prof Ravindra Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“The news, although disappointing for many, is the most appropriate given the speed at which the new variant has spread. The variant has a number of concerning mutations that mean we should control transmission through social restrictions whilst we work to learn more about the impact of these mutations on how the virus behaves.  We should seriously consider regional targeting of the vaccine to control spread.”

 

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MIL OSI United Kingdom