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There are reports of the emerging B.1.1.529 variant, predominantly in southern Africa, which have prompted new infection control measures from the UK government, including that travellers arriving in the UK from several southern African countries will have to quarantine, and from 12:00 UK time on the 26th six countries will be added to the red list with flights temporarily banned.
Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:
“We are learning fast about this new variant, Omicron, and should all be grateful to those who have been so quick to provide information. However, the key to slowing spread is to act early. Many of the questions we are uncertain about will take several weeks to address, but in the meantime sensible measures need to be put into place.
“The reason is that there has been a very rapid increase in case numbers in South Africa, albeit from a low level. The rate at which the variant is detected in South Africa has risen from 1% of samples to 7% over the past six days. In addition, this new variant has many mutations seen in other variants that are present together in this variant (at least 9 mutations from other variants of concern). There are also three new mutations which might alter biological properties of the virus and changes in binding site for antibodies which are used therapeutically. The effect of these mutations on the performance of lateral flow tests are at present unknown.
“It is extremely unlikely that this variant will evade vaccines completely. The vaccines we have are remarkable effective against a range of other variants but we need more lab and real world data to determine the degree of protection in those vaccinated.
“We must not lose sight of the fact that Delta is already taking a big toll in many parts of Europe, including the UK. The NHS is at its limit and we need to get levels of existing virus down. It is vital to get first, second and third doses into arms and to raise levels of immunity right back up. High levels of immunity partially protect even against asymptomatic or mild symptomatic infection for Delta, and almost completely protect against serious disease for Delta. However, vaccines alone are not enough to control this virus. We must continue to wear masks in settings of high transmission risk, to ensure good ventilation and keep at a safe distance from others.
“One of the key factors to emergence of variants may well be low vaccination rates in parts of the world, and the WHO warning that none of us is safe until all of us are safe and should heeded: global vaccine rollout is vital.”
Prof Linda Bauld, Professor of Public Health, University of Edinburgh, said:
“In addition to identifying Omicron as a Variant of Concern, the WHO emphasise measures we can all take to reduce risk. I can’t emphasise these enough. Wear a well fitting mask in many indoor public places, already required in the devolved nations but still voluntary in England. Open windows and doors or check ventilation if you are with others outside of your household, wash your hands regularly with warm water and soap and avoid indoor crowded spaces. Most importantly if anyone has not quite got round to their first or second dose of a vaccine now is the time to take it up. Plus please get your booster when you are eligible – those over 40 can now book online and 16-17 year olds can book appointments for their second dose. We can all do our bit while scientists work at pace to understand this new variant and provide more detailed advice to governments on the options ahead.”
Comments from Prof Wendy Barclay, Prof Neil Ferguson and Dr Tom Peacock; all from Imperial College London:
https://www.imperial.ac.uk/news/232217/qa-imperial-experts-discuss-variant-b11529%E2%80%AF/
Dr Richard Hatchett, CEO of CEPI, the Coalition for Epidemic Preparedness Innovations, said:
“The emergence of a new SARS-CoV-2 variant, B.1.1.529, underscores the critical need for continued COVID-19 vaccine research and development.
“It’s of course critical that we continue to get people vaccinated globally to reduce the amount of virus in circulation, but we must also focus effort and resources on improving the current COVID-19 vaccines to make them more effective against multiple variants of SARS-CoV-2.
“Our strategy must seek to optimize the way we deploy our current vaccines so every dose delivers the maximum benefit; improve upon our existing arsenal of vaccines; and prepare now for the possibility of variants that can evade our vaccines.
“CEPI is funding studies to help policy makers deliver the most effective possible vaccination strategies with the vaccines we have available, like ‘mix-and-match’ vaccination approaches which could lead to stronger and longer lasting protection.
“We’re developing the ‘next-generation’ of vaccines that could offer advantages over the current jabs, like vaccines that target different parts of the virus and a nasal vaccine with the potential to stop transmission.
“And we’re staying one step ahead of the virus by supporting the development of vaccines against variants of concern that we already known about, as well as ‘variant-proof’ vaccines which could protect against a broad range of variants that are yet to emerge but could do so in the future.
“CEPI is also part of a global system designed to pick up these mutants instantly, allowing us to alert our global lab network to start assessing whether current vaccines can block this and future COVID-19 variants, and to alert CEPI-backed developers to look at making variant-proofing updates to their products.”
Prof Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:
“No-one should be surprised by the appearance of a new SARS-CoV-2 variant. The delta variant will be replaced eventually, whether by this latest new variant – B.1.1.529 – or by some other one. Sooner or later we expect to be confronted with a variant that is even more transmissible than delta, or that is better at evading natural and vaccine-induced immunity, or both.
“Genomic surveillance throughout the world is vital for detecting variants as quickly as possible, but that is only the first step – new variants arise all the time and most are not a major concern. Clinical, epidemiological and laboratory studies are needed to establish whether a new variant should be designated a ‘variant of concern’. This takes time, and during that time the variant will be spreading locally and internationally.
“Travel restrictions can delay but not prevent the spread of a highly transmissible variant. If B.1.1.529 is more transmissible than delta then it will arrive in the UK sooner or later; delta spread all over the world earlier this year. The role of travel restrictions is to buy us some time and their value depends on what we do with that time. The priority must be to establish whether B.1.1.529 really does pose a significant threat to public health. If it does then we have a suite of tools available to lessen its impact.
“The notion of ‘living with the virus’ implies living with new variants, and our reaction to any new variant has to be measured, proportionate and sustainable. That is an argument for making travel safer – by enhanced screening and testing – rather than banning travel altogether.”
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
“Only around 11% of the African population have received even one dose of a COVID-19 vaccine. Thus far, much of sub-Saharan Africa have done very well at keeping outbreaks under control, despite their public health and health service resources being extremely limited. For example, Ghana sequencing data showed that the Delta variant arrived there across the summer and did lead to community transmission, yet they have managed to control that outbreak.
“However, with plenty of susceptible populations, it is entirely possible that a COVID-19 outbreak will overwhelm the health services across lower-income settings, and one of the outcomes of that may be further new variants of concern.
“This is one of the consequences of the inequity in vaccine rollouts, and why the grabbing of surplus vaccines by richer countries will inevitably rebound on us all at some point. A fairer global vaccine rollout benefits everyone. We need G20 decision-makers to go beyond vague promises and actually deliver on their commitments to share doses.”
Refs – 11% Africa, https://ourworldindata.org/covid-vaccinations
Also see Ghana, outbreak in July/August was Delta variant https://ourworldindata.org/coronavirus/country/ghana
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, University of Warwick, said:
“This new variant of the COVID-19 virus is very worrying. It is the most heavily mutated version of the virus we have seen to date. This variant carries some changes we’ve seen previously in other variants but never all together in one virus. It also has novel mutations that we’ve not seen before. Some of the mutations that are similar to changes we’ve seen in other variants of concern are associated with enhanced transmissibility and with partial resistance to immunity induced by vaccination or natural infection. This new variant is currently detected at relatively low levels in parts of South Africa but it looks like it’s spreading rapidly.
“At this stage it’s important that we keep a close eye on the spread of this variant and do everything to restrict and delay the arrival of this variant into the UK. We also need laboratory studies to determine whether the antibodies induced by current vaccines are able to block infection with this variant. Variants will continue to be generated as long as the virus is allowed to spread particularly in countries like South Africa where vaccination rates are low. This emphasises the need to control the pandemic at the global level as well as locally and that it is in all our interests to support the roll out of vaccines across the world.”
Prof Sharon Peacock, Director of COG-UK Genomics UK Consortium, and Professor of Public Health and Microbiology, University of Cambridge, said:
“An important body of evidence on a new SARS-COV-2 variant was released yesterday by the South Africa Ministry of Health and supporting scientists. This is referred to as lineage B.1.1.529, and the information can be found here: https://www.youtube.com/watch?v=Vh4XMueP1zQ.
“Although case numbers of COVD-19 in South Africa are low compared with the UK daily count, a rapid increase has been observed in the last 7 days. The number of recorded COVID-19 infections on 16th November 2021 was 273 cases. By 25th November this had risen to more than 1200 cases. More than 80% of these were from Gauteng province. Cases in Gauteng province initially appeared to be clustered, but over time there has been more widespread dispersal of infections across the province.
“An analysis of the R value (a measure of growth rate) is 1.47 for South Africa as a whole, but initial estimates for Gauteng province are 1.93. Based on this measurement, it indicates that growth rate of cases is considerably higher in Gauteng province than the rest of the country.
“The Ministry of Health and scientists in South Africa acted quickly on this information to target genome sequencing of positive samples from people who were PCR test positive in Gauteng province. This identified a new variant B.1.1.529, which has a very unusual constellation of mutations and a mutation profile that is different from known variants of concern. The 1.1.259 variant genome has around 50 mutations, but more than 30 of these are in the spike protein, the region of the protein that interacts with human cells prior to cell entry. The Receptor Binding Motif (the part that binds to our cell receptor called hACE2) has 10 mutations (greater than previous variants of concern).
“Around 100 B.1.1.529 genomes have now been identified in South Africa, mostly from Gauteng province. But this region is also where the sequencing has been targeted, and the question is whether the variant is present over a wider geographic area. The B.1.1.529 has a mutation that leads to ‘S Gene Target Failure’ (or S gene drop out), which means that one of several areas of the gene that are targeted by PCR tests are false negative (the assay remains positive overall if someone has COVID-19). This was also observed with the Alpha variant and can be used as a ‘surrogate marker’, particularly when other circulating lineages are S gene positive (note that Delta is S gene positive by PCR). Using this as a surrogate is not 100% accurate, but it gives a rapid indication from PCR testing before sequencing can be completed and the genome data analysed.
“Analysis of PCR tests in South Africa has shown a rapid increase in S gene target failure PCR tests in numerous provinces. This needs to be confirmed by sequencing, but it suggests that the variant is more widely disseminated in South Africa.
“The epidemiological picture suggests that this variant may be more transmissible, and several mutations are consistent with enhanced transmissibility. Mutations are also present that have been associated in other variants with immune evasion. But the significance of many of the mutations detected, and the combination of these mutations, is not known. Studies are being conducted rapidly in South Africa to look at antibody neutralisation of this variant as well as interactions with T cells. These studies will confirm whether there is reduced immunity in standard lab assays, but these will take several weeks to complete.
“It will also be necessary to get real-world data on whether immunity is reduced to vaccines, and to past infection. There are no data on these important questions at the moment. In the meantime, vaccination should continue to proceed at pace. There is no information on whether the variant leads to a change in disease severity.
“The genetic difference of B.1.1.529 has led to the hypothesis that this may have evolved in someone who was infected but could then not clear the virus, giving the virus the chance to genetically evolve (the equivalent of an evolutionary gym). The same hypothesis was proposed for the Alpha variant, and studies have been done in individual immunocompromised patients that show changes occur in the virus over time, and in response to antibody therapy. But the index (original) case of Alpha was not determined – and trying to pinpoint the index case of a variant of concern does not aid the pandemic response, could be counterproductive by looking back rather than putting all efforts into looking forward, and is to be avoided.
“Looking at variants over time in South Africa, the Beta variant was associated with their second wave of infection, which was replaced by the Delta variant which drove the third wave in South Africa. Initial observations suggest that B.1.1.529 was able to become established in Gauteng province and outcompete Delta. There are several explanations for this. A large super-spreader event linked to B.1.1.529 would give the impression of outcompeting Delta (which is otherwise the ‘fittest’ variant we have seen to date). But the other explanation is that B.1.1.529 can actually outcompete Delta. Further studies are required to confirm this.
“Lineage B.1.1.529 has also very recently been detected in Botswana (n=4) and Hong Kong (n=1, in a traveller from South Africa). No cases have been confirmed in the UK. It is important not to assume that the variant first emerged in South Africa.
“In summary, the full significance of this variant is not known.
“Aspects of concern are: 1. the rapid increase in cases in Gauteng province with a raised R value, linked to the detection of a new variant; 2. the detection of putative cases across numerous provinces in South Africa based on a PCR test with S Gene Target Failure, consistent with the new variant; 3. the variant may be outcompeting the Delta variant, suggesting that it is ‘fitter’; 4. a very large number of mutations are present in the spike protein, some of which have been associated previously with increased transmission and immune evasion. Many mutations are not familiar to us (not characterised).
“Numerous questions remain unanswered, including disease severity, and immune evasion in lab tests and real life. Increased transmissibility also needs to be formally assessed. The evidence so far (or lack of it) would mean that this would not be categorised as a variant of concern today based on established criteria.
“This situation is reminiscent of the epidemiology of Alpha in Kent around a year ago. There was a surge in cases, but it was not clear whether this was due to one or more super-spreader events or was associated with a more transmissible virus. The important difference now is that we have effective vaccines, and considerable learning about variants has also accumulated since then.
“There are two approaches to what happens next: wait for more scientific evidence – or act now and row back later if it wasn’t required. I believe that it is better to ‘go hard, go early and go fast’ and apologise if mistaken, than to take an academic view that we need to reach a tipping point in evidence before action is taken. Rapid spread in South Africa could be due to super-spreader events or other factors. But there are sufficient red flags to assume the worst rather than hope for the best – and take a precautionary approach.
“The news overnight that the UK government is taking action over border controls represents appropriate caution in my view. I understand from breaking news that all flights from South Africa, Namibia, Zimbabwe, Botswana, Lesotho and Eswatini are being suspended, and the six countries are being added to the red list with hotel quarantine being used from Sunday. It is likely to prove easier to de-escalate from this position than it would be to control a new variant if it was introduced into the UK where transmission and daily high rates of COVID-19 are already high, and the NHS is under pressure. This is a dynamic situation, and more information will emerge daily from South Africa and elsewhere.
“This event once again highlights the continued importance and need for genomic surveillance of SARS-CoV-2 and access to relevant samples to do this. Sequencing is performed using PCR positive samples and cannot be performed using a positive lateral flow test. It will also be important to heighten sequencing of samples from people with a positive PCR test plus a travel history, sequencing of new COVID-19 clusters and areas with a rapid surge in cases, together with ongoing random sequencing across the wider population of people with COVID-19.
“Surveillance of PCR tests across the UK and elsewhere to detect samples with S gene target failure, with rapid sequencing of these, will no doubt already be swinging into place.
“The South African Ministry Health and their excellent scientists are to be applauded in their response, their science, and in sounding the alarm to the world. It is to their credit that they have developed an excellent sequencing capability, and are sharing their expertise with others in their region. But many countries in the world do not have the ability to undertake genomic surveillance. Ongoing efforts to improve this situation, combined with a quantum leap in access to vaccination in countries where vaccine access is low, remains vital to control of the pandemic worldwide.”
Prof Francois Balloux, Professor of Computational Systems Biology and Director, UCL Genetics Institute, UCL, said:
What do we know about the mutations the B.1.1.529 variant has?
“B.1.1.529 carries a large number of mutations relative to other lineages, including around 30 in the spike protein. Several of those mutations have been observed in previous Variants of Concern and/or have been associated with partial immune escape. Some of those mutations have rarely been observed together in the same strain before.
How confident can we be in knowing what the impact of these mutations could be?
“From the suite of mutations, we can expect that B.1.1.529 is less well recognised by neutralising antibodies, (i.e. the antibodies that bind to the spike protein and thus precluding attachment to host cells and hence infection). As such, we anticipate B.1.1.529 is more likely to (re-)infect people who acquired immunisation from vaccination and previous infection. At this stage, we cannot make any robust prediction based on its genetic makeup alone about its expected transmissibility or virulence.
What risks are so far theoretical and what are evidence-based?
“The biggest risk would be that B.1.1.529 is better at (re-) infecting immunised people, as well as more transmissible and virulent. B.1.1.529 seems to be spreading fast in South Africa but so far we cannot assess whether this may be caused by a higher rate of (re-)infection of people who have been immunised or may be due to higher intrinsic transmissibility.
What makes the situation in South African so concerning re what has happened there in recent days?
“The number of B.1.1.529 infections reported in South Africa has increased sharply over recent days.
How can this variant be detected / monitored?
“Besides whole genome sequencing, the B.1.1.529 lineage can be easily diagnosed with high through-put screening. In particular, it can be detected by routine qPCR protocols as it carries a deletion in the Spike protein at positions 69-70 that precludes attachment of one of the PCR primers (same as alpha, which is now virtually extinct).
Could this variant fit the criteria for a Variant of Concern?
“Based on the limited evidence available so far, B.1.1.529 probably qualifies as a Variant of Concern. It will likely be elevated to that status before the end of the week. It would be assigned the Greek letter nu (ν).
What do we know, and not yet know, about how the mutations on this variant might impact things like transmissibility, severity, and immune protection from either previous infection or vaccination?
“Based on its genetic makeup, we can confidently predict B.1.1.529 may partly bypass immunisation provided by vaccination and prior infection. Any prediction about its transmissibility and virulence feels premature. While we can work out the contribution to transmissibility and virulence of mutations in isolation, we still struggle to accurately predict their effect when found in combination.
Are there similarities or differences between the population in South Africa and that here in the UK (such as level of vaccination, previous infection, demographics, etc.)?
“The epidemiological situations in South Africa and the UK are drastically different. South Africa experienced high rates of infection but vaccination rates remain low (~24%). The South African population is also younger on average.
Are scientists worried? Should the UK public be alarmed?
“The emergence and spread of a lineage as or more transmissible than delta, and additionally capable of partial immune escape would be a cause of concern. Scientists and politicians should try to keep a cool head, and I can see no benefit in the UK public being alarmed.
Are the travel restrictions announced last night proportionate and evidence-based?
“B.1.1.529 was likely detected fairly soon after its emergence thanks to the remarkable genomic surveillance in place in Botswana and South Africa. The objective of the border closures and travel restrictions that have been announced is to limit the global spread of the variant. If B.1.1.529 were more transmissible than delta, this strategy is most unlikely to succeed in the long-term, but might allow gaining some time to further increase vaccination rates (including third doses), and deploy promising drugs currently in the pipeline
Is there any evidence this variant exists in countries outside those it has been identified in so far?
“B.1.1.529 has been detected so far in Botswana and South Africa, and in one incoming traveller from South Africa in Hong Kong.
Any other comments about this development?
“B.1.1.529 could well represent another setback after the emergence and global spread of the alpha and delta variants. That said, B.1.1.529 is most unlikely to fully escape immunisation provided by vaccination and prior infection. The objective now should be to further increase vaccination rates, including administration of a third dose for anyone most at risk. With high vaccination rates and promising drugs on the horizon, a possible B.1.1.529 wave should be far less painful to weather than the alpha and delta ones.”
Prof Neil Ferguson, Director of the MRC Centre for Global Infectious Disease Analysis, Imperial College London, said:
“The B.1.1.529 variant has an unprecedented number of mutations in the Spike protein gene, the protein which is the target of most vaccines. There is therefore a concern that this variant may have a greater potential to escape prior immunity than previous variants. It is also concerning that this variant appears to be driving a rapid increase in case numbers in South Africa. The Government’s move to restrict travel with South Africa is therefore prudent. However, we do not yet have reliable estimates of the extent to which B.1.1.529 might be either more transmissible or more resistant to vaccines, so it is too early to be able to provide an evidence-based assessment of the risk it poses. Addressing that gap is a top priority of researchers in South Africa and their partners around the world, including at Imperial College.”
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Comments issued on the 25th before the news that night of travel restrictions being brought in:
Prof Ewan Birney, Deputy Director General of EMBL and Director of EMBL’s European Bioinformatics Institute (EMBL-EBI), said:
“Early evidence from genomic surveillance in South Africa suggests that B.1.1.529 is a serious cause for concern. The South African surveillance and epidemiology groups should be commended for their timely data collection, analysis and transparency.
“Armed by our experience and understanding of the Alpha and Delta variants, we know that early action is far better than late action. It may turn out that this variant is not as large a threat as Alpha and Delta, but the potential consequences of not acting on the possibility it could be are serious.
“Measures to prevent this variant of concern from spreading include implementing appropriate quarantine and PCR testing measures and sequencing on international travel from Southern Africa and continue careful monitoring of the circulating SARS-CoV-2 variants. The international community should get drugs and vaccines to South Africa as soon as possible. All countries should remain vigilant and share SARS-CoV-2 genomes.”
Prof Ravi Gupta, Professor of Clinical Microbiology, University of Cambridge, said:
“B.1.1.529 has signatures of cumulative mutation indicating that it emerged in a chronic infection.
“B.1.1.529 does certainly look of significant concern based on mutations present. Many have been shown to impact binding by neutralising antibodies, and some are known to increase the ability of virus to enter cells or to make them fuse together to allow cell-cell spread.”
https://twitter.com/sajidjavid/status/1463973520497684480?s=20
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests
Prof Sharon Peacock: “Views are my own.”
None others received.