Lineage B.1.1.7, also known as 20I/501Y.V1, Variant of Concern 202012/01 (VOC-202012/01) or commonly as the UK variant or British variant, 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 40%–80% (with most estimates lying around the middle-to-higher end of this range) 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 they dubbed Variant of Concern 202102/02 (VOC-202102/02). This mutation is also present in the South Africa and Brazil variants and may reduce vaccine effectiveness.
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 after Kent, where the variant was found.
In scientific use, the variant had originally been named the first Variant Under Investigation in December 2020 (VUI – 202012/01) by Public Health England (PHE), 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 PHE 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, dubbed it lineage B.1.1.7, while Nextstrain dubbed the variant 20I/501Y.V1.
B.1.1.7 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 B.1.1.7 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 RT-PCR test used predominantly in the UK, Thermo Fisher's TaqPathCOVID-19. The test matches RNA in three locations, and stopped working for the spike gene due to the HV 69–70 deletion—a deletion of the amino acids histidine and valine in positions 69 and 70, respectively, of the spike protein—in B.1.1.7's spike protein. This made preliminary identification easier because it could be better suspected which cases were with B.1.1.7 through 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.
Mutations in SARS-CoV-2 are common: over 4,000 mutations have been detected in its spike protein alone, according to the COVID-19 Genomics UK (COG-UK) Consortium. 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).
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.On 9 February 2021, it became known that some 76 cases with the E484K mutation had been detected, principally in Bristol, but with a genomically distinct group in Liverpool also carrying the mutation. A week later a Research and analysis report from PHE gave a total of 77 confirmed and probable cases involving the E484K mutation across the UK, in two variants, VUI-202102/01 and VOC-202102/02, the latter described as 'B.1.1.7 with E484K'.
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 calculated it to be 55% (48%–62%) more transmissible in Denmark based upon the observed development of its relative frequency from 4 January to 12 February 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—i.e., 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.
One of the most important changes in B.1.1.7 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". In early 2021 a peer-reviewed paper found that the mentioned HV 69–70 deletion "appeared to have two-fold higher infectivity over a single round of infection compared to [wild-type SARS-CoV-2]" in lentiviral SARS-CoV-2 pseudoviruses.
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 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.
In a paper analysing twelve different studies on the B.1.1.7 death rate relative to non-B.1.1.7 variants, it was found to have a higher death rate (71% according to LSHTM, 70% according to University of Exeter, 65% according to Public Health England, and 36% according to Imperial College London), and NERVTAG concluded that "it is likely that infection with VOC B.1.1.7 is associated with an increased risk of hospitalisation and death compared to infection with non-VOC viruses". Results of the death studies were associated with some high uncertainty and confidence intervals, because of a limitted sample seize related to the fact that UK only analyzed the VOC status for 8% of all COVID-19 deaths.
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", that "SARS-CoV-2 ORF8 mediates major histocompatibility complex I (MHC-I) degradation", and that "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". The HV 69–70 deletion 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 the virus by providing the means to rapidly identify large numbers 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.
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 VOC-202012/01 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 in the UK:
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 B.1.1.7. By 25 January 2021, the number of confirmed and probable UK cases had grown to 28,122.
Spread in North America:
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 1881 cases in 45 US states found by February 23 (being most prevalent in Florida, Michigan and California). The first comprehensive national study estimated 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. Data from the Helix Research Team, later determined the actual values for week 4 by multiplying each days "SGTF percentage of positive samples" with the "B.1.1.7 variant share of all sequenced SGTF positives", and found the variant at a rate of 7.7% in Florida, 2.9% in US and 2.0% in California. 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. In Canada, the variant first appeared in Ontario late December 2020. By February 13, it had spread to all ten provinces.