Variant of Concern 202012/01, abbreviated VOC-202012/01 (also known as lineage B.1.1.7, 20I/501Y.V1 or commonly as the UK variant or British variant; see § Names), is a variant of SARS-CoV-2, the virus that causes COVID-19. One of several variants believed to be of particular importance, it is estimated to be 30%–80% more transmissible than wild-type SARS-CoV-2 and was detected in November 2020 from a sample taken in September, during the COVID-19 pandemic in the United Kingdom; it began to spread quickly by mid-December, and is correlated with a significant increase in SARS-CoV-2 infections in the country. This increase is thought to be at least partly because of one or more mutations in the virus's spike protein. The variant is also notable for having more mutations than normally seen.
As of January 2021, more than half of all genomic sequencing of SARS-CoV-2 was carried out in the UK. This has given rise to questions as to the variant's origins, and how many other important variants may be circulating around the world.
On 2 February 2021, Public Health England reported that they had detected "[a] limited number of B.1.1.7 VOC-202012/01 genomes with E484K mutations", which is also present in the South Africa and Brazil variants; this mutation may reduce vaccine effectiveness.
Names
The variant is known by several names. In British-government and media reports it may be referred to as UK COVID-19 variant, UK coronavirus variant, the new variant or, particularly outside the UK, as the UK variant or British variant. It is sometimes called the Kent variant, with no further explanation.
In scientific use the variant had originally been named the first Variant Under Investigation in December 2020 (VUI – 202012/01) by Public Health England, but was reclassified to a Variant of Concern (Variant of Concern 202012/01, abbreviated VOC-202012/01) by Meera Chand and her colleagues in a report published by Public Health England on 21 December 2020. In a report written on behalf of COVID-19 Genomics UK (COG-UK) Consortium, Andrew Rambaut and his co-authors, using the Phylogenetic Assignment of Named Global Outbreak Lineages (PANGOLIN) tool, referred to the variant as lineage B.1.1.7, while Nextstrain dubbed the variant 20I/501Y.V1.
Detection
VOC-202012/01 was first detected in early December 2020 by combining genome data with knowledge that the rates of infection in Kent were not falling despite national restrictions.
The two earliest genomes that belong to the B.1.1.7 lineage were collected on 20 September 2020 in Kent and another on 21 September 2020 in Greater London. These sequences were submitted to the GISAID sequence database (sequence accessions EPI_ISL_601443 and EPI_ISL_581117 respectively).
Backwards tracing using genetic evidence suggests VOC-202012/01 emerged in September 2020 and then circulated at very low levels in the population until mid-November. The increase in cases linked to the variant first became apparent in late November when Public Health England (PHE) was investigating why infection rates in Kent were not falling despite national restrictions. PHE then discovered a cluster linked to this variant spreading rapidly into London and Essex.
Also important was the nature of the PCR test used predominantly in the UK, Thermo Fisher's TaqPathCOVID-19. The test matches RNA in three locations, and stopped working for one of these sections due to the HV 69–70 deletion. This made preliminary identification easier, which could be confirmed with genome sequencing.
Although the variant was first detected in Kent, it may never be known where it originated. Discovery in the UK may merely reflect that the UK does more sequencing than many other countries. It has been suggested that the variant may have originated in a chronically infected immunocompromised person, giving the virus a long time to replicate and evolve.
Characteristics
Genetics
VOC-202012/01 is defined by 23 mutations: 14 non-synonymous mutations, 3 deletions, and 6 synonymous mutations (i.e., there are 17 mutations that change proteins and six that do not).Mutations in SARS-CoV-2 are common: over 4,000 mutations have been detected in the spike glycoprotein alone, according to the COVID-19 Genomics UK (COG-UK) Consortium.
E484K mutation
On 2 February 2021, Public Health England reported that they had detected "[a] limited number of B.1.1.7 VOC-202012/01 genomes with E484K mutations", which is also present in the South Africa and Brazil variants; this mutation may reduce vaccine effectiveness.
Transmissibility
Estimates of VOC-202012/01's transmissibility have varied greatly across different studies: in a preprint, the Centre for the Mathematical Modelling of Infectious Diseases at the London School of Hygiene & Tropical Medicine reported that the variant was 56% (50%–74%) more transmissible than other variants across three regions in England (East of England, South East of England, and London) in early December 2020, while a peer-reviewed article concluded that it was 75% (70%–80%) more transmissible in the UK between October and November 2020. The Dutch Ministry of Health, Welfare and Sport calculated that the variant was 40% more transmissible in the Netherlands from 7 to 21 January 2021; the Danish Statens Serum Institut found it to be 55% (40%–70%) more transmissible in Denmark around mid-January 2021.
On 18 December 2020—early on in the risk assessment of the variant—the UK scientific advisory body New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) concluded that they had moderate confidence that VOC-202012/01 was substantially more transmissible than other variants, but that there were insufficient data to reach any conclusion on underlying mechanism of increased transmissibility (e.g. increased viral load, tissue distribution of virus replication, serial interval etc.), the age distribution of cases, or disease severity. Data seen by NERVTAG indicated that the relative reproduction number ("multiplicative advantage") was determined to be 1.74, that is, that the variant is 74% more transmissible, assuming a 6.5-day generational interval. It was demonstrated that the variant grew fast exponentially with respect to the other variants. The variant out-competed the ancestral variant by a factor of every two weeks. Another group came to similar conclusions, generating a replicative advantage, independent of "protective measures", of 2.24 per generation of 6.73 days, out-competing the ancestral variant by every two weeks. Similarly, in Ireland, the variant—as indicated by the historically rare missing S-gene detection (S-gene target failure [SGTF])—went from 16.3% to 46.3% of cases in two weeks. This demonstrates, based on the statistics of 116 positive samples, that a relative growth during that time of occurred, when accounting for the declining percentage of the other variants. The variant became the dominant variant in London, East of England and the South East from low levels in one to two months. A surge of SARS-CoV-2 infections around the start of the new year is seen as being the result of the elevated transmissibility of the variant, while the other variants were in decline.
One of the most important changes in VOC-202012/01 seems to be N501Y, a change from asparagine (N) to tyrosine (Y) in amino-acid position 501. This is because of its position inside the spike protein's receptor-binding domain (RBD)—more specifically inside the receptor-binding motif (RBM), a part of the RBD—which binds human ACE2. Mutations in the RBD can change antibody recognition and ACE2 binding specificity and lead to the virus becoming more infectious; indeed, Chand et al. concluded that "[i]t is highly likely that N501Y affects the receptor-binding affinity of the spike protein, and it is possible that this mutation alone or in combination with the deletion at 69/70 in the N-terminal domain (NTD) is enhancing the transmissibility of the virus".
The CDC has presented epidemiological models, assuming 50% more transmissibility than current U.S. variants, that infer B.1.1.7 would become the predominant variant in March 2021.
Virulence
NERVTAG concluded on 18 December 2020 that there were insufficient data to reach a conclusion regarding disease severity. At prime minister Boris Johnson's briefing the following day, officials said that there was "no evidence" as of that date that the new variant caused higher mortality, or was affected differently by vaccines and treatments; Vivek Murthy agreed with this. Susan Hopkins, the joint medical adviser for the NHS Test and Trace and Public Health England (PHE), declared in mid-December 2020: "There is currently no evidence that this strain causes more severe illness, although it is being detected in a wide geography, especially where there are increased cases being detected." Around a month later, however—on 22 January 2021—Johnson said that "there is some evidence that the new variant [VOC-202012/01] [...] may be associated with a higher degree of mortality", though Sir Patrick Vallance, the government's Chief Scientific Advisor, stressed that there is not yet enough evidence to be fully certain of this. Neil Ferguson of NERVTAG told ITV News: "Four groups—Imperial, LSHTM, PHE and Exeter—have looked at the relationship between people testing positive for the variant vs old strains and the risk of death; that suggests a 1.3-fold increased risk of death." In a paper analysing different studies on VOC-202012/01 death rate, NERVTAG concluded that "[t]here is a realistic possibility that VOC B.1.1.7 is associated with an increased risk of death compared to non-VOC viruses".
Genetic sequencing of VOC-202012/01 has shown a Q27stop mutation which "truncates the ORF8 protein or renders it inactive". An earlier study of SARS-CoV-2 variants which deleted the ORF8 gene noted that they "have been associated to milder symptoms and better disease outcome". The study also noted that "SARS-CoV-2 ORF8 is an immunoglobulin (Ig)–like protein that modulates pathogenesis", "SARS-CoV-2 ORF8 mediates major histocompatibility complex I (MHC-I) degradation", and "SARS-CoV-2 ORF8 suppresses type I interferon (IFN)–mediated antiviral response".
Referring to amino-acid position 501 inside the spike protein (VOC-202012/01 has a mutation, N501Y, in this position), Chand et al. concluded that "it is possible that variants at this position affect the efficacy of neutralisation of virus", but noted that "[t]here is currently no neutralisation data on N501Y available from polyclonal sera from natural infection". 69–70del—a deletion of the amino acids in positions 69–70 of the spike protein—has, however, been discovered "in viruses that eluded the immune response in some immunocompromised patients", and has also been found "in association with other RBD changes".
Rapid-antigen-test effectiveness
Several rapid antigen tests for SARS-CoV-2 are in widespread use globally for COVID-19 diagnostics. They are believed to be useful in stopping the chain of transmission of SARS-CoV-2 by providing the means to rapidly identify large number of cases as part of a mass testing program. Following the emergence of VOC-202012/01, there was initially concern that rapid tests might not detect it, but Public Health England determined that rapid tests evaluated and used in the United Kingdom detect the variant.
Vaccine effectiveness
As of late 2020, several COVID-19 vaccines were being deployed or under development.
However, as further mutations occur, concerns were raised as to whether vaccine development would need to be altered. SARS-CoV-2 does not mutate as quickly as, for example, influenza viruses, and the new vaccines that had proved effective by the end of 2020 are types that can be adjusted if necessary. As of the end of 2020, German, British, and American health authorities and experts believe that existing vaccines will be as effective against the new VOC-202012/01 variant as against previous variants.
On 18 December, NERVTAG determined "that there are currently insufficient data to draw any conclusion on [...] [a]ntigenic escape".
As of 20 December 2020, Public Health England confirmed there is "no evidence" to suggest that the new variant would be resistant to the Pfizer–BioNTech vaccine currently being used in the UK's vaccination programme, and that people should still be protected.
Spread
Cases of VOC-202012/01 are likely to be undetected in most countries as most tests do not distinguish between this variant and other SARS-CoV-2 variants, and as many SARS-CoV-2 infections are not detected at all. RNA sequencing is required for detection of this variant, although variant-specific PCR testing is becoming available.
The first case was likely in mid-September 2020 in London or Kent, United Kingdom. As of 13 December 2020, 1,108 cases with this variant had been identified in the UK in nearly 60 different local authorities. These cases were predominantly in the south east of England. The variant has also been identified in Wales and Scotland. By November, around a quarter of cases in the COVID-19 pandemic in London were being caused by the new variant, and by December, that was a third. In mid-December, it was estimated that almost 60 percent of cases in London involved VOC-202012/01. By 25 January 2021, the number of confirmed and probable UK cases had grown to 28,122.
The variant became dominant for:
- United Kingdom in week 52 of 2020.
- Ireland in week 2 of 2021.
Also in Slovakia, 74% of cases was of the variant on February 3. In Israel the variant was estimated to account for 30% to 40% of infections on January 19. In the Netherlands, the variant accounted for 24.1% of cases in week 3, and it probably became dominant around January 31. In Portugal, the variant represented 16.0% of the 10–19 January infections, followed by 22.5% in week 3 and a forecast of becoming dominant in week 5. In Belgium 25% of cases were of the variant as of January 24. In Denmark the variant grew from 0.3% (week 46) to 19.9% (week 4), and is expected to become dominant (over 50%) around mid-February and comprise around 80% of the total circulating variants by early March. In Switzerland, the variant grew to 15.8% of cases in week 4. In France the variant grew from a share of 3.3% on January 7-8 to 14.0% on January 27, with the expectation of becoming dominant around week 8-11 of 2021. In Sweden the variant share was found to be 11% for week 4 across four of its southern regions (Skåne, Västmanland, Västra Götaland, and Gävleborg), and would under the assumption of 50% increased transmissibility compared to the original virus become dominant around week 12-14. In Spain, an estimated 5 to 10% of cases are of the variant as of January 29. In Germany an estimated 6% of cases are of the variant early February.
In the United States, the variant first appeared late November 2020, grew to 0.3% at the start of 2021, and was expected to become predominant in March 2021. The number of variant cases in the US confirmed by genome sequence, grew from 76 cases in 12 US states found by January 13, to 932 cases in 34 US states found by February 9 (being most prevalent in Florida and California). The first comprehensive national study found the variant share in week 4 to be 2.1% for the US (with expected dominance March 23), 2.0% for California (with expected dominance April 5), 4.5% for Florida (with expected dominance March 8), and unknown values for other states due to lack of sufficient data.
The relatively low sensitivity of the projected dominance dates to the current percentage of the variant is due to its fast relative exponential growth. It is presumed the variant will become dominant over the ancestral variant globally, although it may be taken over by other variants.
| hideDevelopment of the B.1.1.7 lineage (share of analyzed SARS-CoV-2–positive tests in a given week) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Country | Week 43 | Week 44 | Week 45 | Week 46 | Week 47 | Week 48 | Week 49 | Week 50 | Week 51 | Week 52 | Week 53 | Week 1 | Week 2 | Week 3 | Week 4 | Week 5 |
| England | 0.5% | 1.2% | 1.5% | 5.3% | 7.8% | 11.4% | 22.1% | 38.1% | 61.8% | 62.1% | 78.4% | 76.7% | 79.7% | – | – | – |
| United Kingdom | 0.3% | 0.8% | 2.6% | 6.3% | 10.9% | 10.1% | 14.0% | 33.3% | 48.3% | 53.9% | 69.3% | – | – | – | – | – |
| Ireland | – | – | 1.9% (few data) | 0.0% (few data) | 0.0% (few data) | 6.1% (few data) | 2.2% (few data) | 1.6% | 7.5% | 16.3% | 26.2% | 46.3% | 57.7% | 62.8% | – | – |
| Netherlands | – | – | – | – | – | – | 1.1% | 0.7% | 1.1% | 1.4% | 5.2% | 8.8% | 19.8% | 24.1% | – | – |
| Portugal | – | – | – | – | – | – | 1.7% | 1.0% | 1.5% | 2.0% | 2.9% | 7.0% | 12.2% | 22.5% | – | – |
| Denmark | – | – | – | 0.3% | 0.0% | 0.2% | 0.2% | 0.4% | 0.8% | 2.0% | 2.3% | 3.9% | 7.5% | 12.7% | 19.9% | – |
| Switzerland | – | – | – | – | – | – | – | – | 0.04% | 0.4% | 0.8% | 2.7% | 4.9% | 8.7% | 15.8% | 23.5% |
| France | – | – | – | – | – | – | – | – | – | – | – | 3.3% | – | – | 14.0% | – |
| Sweden | – | – | – | – | – | – | – | – | – | – | – | – | – | – | 11.4% | – |
| Florida | – | – | – | – | – | – | – | – | 0.3% | 0.5% | 0.7% | 1.0% | 2.2% | 3.8% | 4.5% | – |
| United States | – | – | – | – | – | – | – | – | 0.05% | 0.2% | 0.3% | 0.5% | 0.9% | 1.5% | 2.1% | – |
| California | – | – | – | – | – | – | – | – | – | 0.3% | 0.4% | 1.0% | 1.1% | 1.4% | 2.0% | – |
The following additional countries are likely to have a significant share present, due to their finding more than 50 cases through genome sequencing, but have not yet calculated their variant share: Italy (169 cases), Austria (140 cases), Turkey (116 cases) and Australia (71 cases).[1]
Countries reporting a first case appearance
Cases of the variant began to be reported globally during December, being reported in Denmark, Belgium, the Netherlands, Australia and Italy. Shortly after, several other countries confirmed their first cases, the first of whom were found in Iceland and Gibraltar, then Singapore, Israel and Northern Ireland on 23 December, Germany and Switzerland on 24 December, and the Republic of Ireland and Japan confirmed on 25 December.
The first cases in Canada, France, Lebanon, Spain and Sweden were reported on 26 December. Jordan, Norway, and Portugal reported their first case on 27 December, Finland and South Korea reported their first cases on 28 December, and Chile, India, Pakistan and the United Arab Emirates reported their first cases on 29 December. The first case of new variant in Malta and Taiwan are reported on 30 December. China and Brazil reported their first cases of the new variant on 31 December. The United Kingdom and Denmark are sequencing their SARS-CoV-2 cases at considerably higher rates than most others, and it was considered likely that additional countries would detect the variant later.
The United States reported a case in Colorado with no travel history on 29 December, the sample was taken on 24 December. On 6 January 2021, the US Centers for Disease Control and Prevention announced that it had found at least 52 confirmed cases in California, Florida, Colorado, Georgia, and New York. In the following days, more cases of the variant were reported in other states, leading former CDC director Tom Frieden to express his concerns that the U.S. will soon face "close to a worst-case scenario".
Turkey detected its first cases in 15 people from England on 1 January 2021. It was reported on 1 January that Denmark had found a total of 86 cases of the variant, equalling an overall frequency of less than 1% of the sequenced cases in the period from its first detection in the country in mid-November to the end of December? this had increased to 1.6% of sequenced tests in the period from mid-November to week two of 2021, with 7% of sequenced tests in this week alone being of the B.1.1.7 lineage. Luxembourg and Vietnam reported their first case of this variant on 2 January 2021.
On 3 January 2021, Greece and Jamaica detected their first four cases of this variant and Cyprus announced that it had detected VOC-202012/01 in 12 samples. At the same time, New Zealand and Thailand reported their first cases of this variant, where the former reported six cases made up of five from the United Kingdom and one from South Africa, and the latter reported the cases from a family of four who had arrived from Kent. Georgia reported its first case and Austria reported their first four cases of this variant, along with one case of 501.V2 variant, on 4 January.
On 5 January, Iran, Oman, and Slovakia reported their first cases of VOC-202012/01. On 8 January, Romania reported its first case of the variant, an adult woman from Giurgiu County who declared not having left the country recently. On 9 January, Peru confirmed its first case of the variant. Mexico and Russia reported their first case of this variant on 10 January, then Malaysia and Latvia on 11 January.
On 12 January, Ecuador confirmed its first case of this variant. The Philippines and Hungary both detected the presence of the variant on 13 January. The Gambia recorded first cases of the variant on 14 January with it being the first confirmation of the variant's presence in Africa. On 15 January, the Dominican Republic confirmed its first case of the new variant and Argentina confirmed its first case of the variant on 16 January. Czech Republic and Morocco reported their first cases on 18 January and Kuwait confirmed its first cases of the variant on 19 January. Nigeria confirmed its first case on 25 January. On 28 January, Senegal detected its first case of the variant. On 4 February, health authorities in Uruguay announced the first case of the variant in the country. The case was detected in a person who entered the country on 20 December 2020 and has been in quarantine ever since.
In early January, an outbreak linked to a primary school led to the detection of at least 30 cases of the new variant in the Bergschenhoek area of the Netherlands, signifying local transmission.
On 16 January, the Los Angeles County Department of Public Health confirmed the variant was detected in L.A. County, with public health officials believing that it is spreading in the community.
N501Y mutation
A variant with the same N501Y mutation (which may result in higher transmissibility), but with a separate lineage from the UK variant, was detected in South Africa, and named 501.V2. The N501Y mutation has also been detected elsewhere: in Australia in June–July, in the US in July, and in Brazil (B.1.1.28 in April and B.1.1.248 since), and it is not yet clear if it arose spontaneously in the UK, or was imported.
Control
In the presence of an extra infectious variant, stronger physical distancing and lockdown measures were opted for to avoid overwhelming the population due to its tendency to grow exponentially.
All countries of the United Kingdom were affected by domestic travel restrictions in reaction to the increased spread of COVID-19—at least partly attributed to VOC-202012/01—effective from 20 December 2020. During December 2020, an increasing number of countries around the world either announced temporary bans on, or were considering banning, passenger travel from the UK, and in several cases from other countries such as the Netherlands and Denmark. Some countries banned flights; others allowed only their nationals to enter, subject to a negative SARS-CoV-2 test. A WHO spokesperson said "Across Europe, where transmission is intense and widespread, countries need to redouble their control and prevention approaches". Most bans by EU countries were for 48 hours, pending an integrated political crisis response meeting of EU representatives on 21 December to evaluate the threat from the new variant and coordinate a joint response.
Many countries around the world imposed restrictions on passenger travel from the United Kingdom; neighbouring France also restricted manned goods vehicles (imposing a total ban before devising a testing protocol and permitting their passage once more). Some also applied restrictions on travel from other countries. As of 21 December 2020, at least 42 countries had restricted flights from the UK, and Japan was restricting entry of all foreign nationals after cases of the new variant were detected in the country.
The usefulness of travel bans has been contested as limited in cases where the variant has likely already arrived, especially if the estimated growth rate per week of the virus is higher locally.
Notes
- Written as VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) by GISAID and the ECDC.
- This redesignation is explained in the report:
- SARS-CoV-2's S gene encodes its spike protein.
- In Sweden, a study comprising 11% of all positive samples nationwide for week 4, found the B.1.1.7 share to be 11.4% (250/2200). Samples were however only collected from four southern regions (Skåne, Västmanland, Västra Götaland, and Gävleborg). The national authorities plan to expand the study to cover more/all regions for the following weeks in February 2021.
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