Variant of Concern 202012/01

"B117" redirects here. For other uses, see B117 (disambiguation).

File:202012 01 Outbreak World Map.png

Countries with confirmed cases of VOC-202012/01 as of 18 January 2021.
Legend:

  1000+ confirmed cases

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Variant of Concern 202012/01 (VOC-202012/01; also known as lineage B.1.1.7 or 20B/501Y.V1, see other names below) is a variant of SARS-CoV-2, the virus that causes COVID-19, one of several causing concern. It is estimated to have first emerged in September 2020 during the COVID-19 pandemic in the United Kingdom; it was studied in November and it began to spread quickly by mid-December. It is correlated with a significant increase in the rate of COVID-19 infections in the United Kingdom; this increase is thought to be at least partly because of change N501Y (see nomenclature for mutations) inside the spike glycoprotein's receptor-binding domain, which binds ACE2 in human cells. The variant is also notable for having more mutations than the recorded trend to date.

Names

The variant is known by several names. In government and media reports it may be referred to as UK COVID-19 variant UK coronavirus variant, and, in UK news media, "the Kent variant", among other names. In January 2021, German chancellor Angela Merkel referred to the variant as the "British virus".

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) 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 referred to the variant as lineage B.1.1.7, while Nextstrain dubbed the variant 20B/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). As of 15 December, there were 1623 genomes in the B.1.1.7 lineage. Of these 519 were sampled in Greater London, 555 in Kent, 545 in other regions of the UK including both Scotland and Wales, and 4 in other countries.

Backwards tracing using genetic evidence suggests this new variant emerged in September 2020 and then circulated at very low levels in the population until mid-November. The increase in cases linked to the new 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.

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

(change of amino acid only)

Defining mutations in VOC-202012/01

Gene	Nucleotide	Amino acid
ORF1ab	C3267T	T1001I
	C5388A	A1708D
	T6954C	I2230T
	11288–11296del	SGF 3675–3677del
Spike	21765–21770del	HV 69–70del
	21991–21993del	Y144del
	A23063T	N501Y
	C23271A	A570D
	C23604A	P681H
	C23709T	T716I
	T24506G	S982A
	G24914C	D1118H
ORF8	C27972T	Q27stop
	G28048T	R52I
	A28111G	Y73C
N	28280 GAT→CTA	D3L
	C28977T	S235F
Source: Chand et al. (), table 1 (p. 5)

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.

The VOC-202012/01 variant is defined by 23 mutations: 13 non-synonymous mutations, 4 deletions, and 6 synonymous mutations (i.e., there are 17 mutations that change proteins and six that do not).

Transmissibility

The UK scientific advisory body NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group) concluded on 18 December 2020 that they had moderate confidence that VUI-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. The variant will thus out-compete the ancestral variant by a factor of $1.74^{(14/6.5)}=3.3$ 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 $2.24^{14/6.73}=5.4$ every two weeks. 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.

The variant has taken off in Ireland where it has shown a similar advantage, and appears to become dominant imminently. It also grows fast in continental Western Europe, and is expected there to be dominant somewhere in February. In the US this is expected to occur in March. It is presumed the variant will become dominant globally. It requires tougher restrictions to avoid fast exponential growth of a virus which is this transmissible, and transmission control of this variant looks increasingly tenuous.

One of the most important changes in VOC-202012/01 seems to be N501Y, a change from asparagine (N) to tyrosine (Y) at amino-acid site 501. This is because of its position inside the spike glycoprotein'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. conclude 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".

UK Prime Minister Boris Johnson said on 19 December 2020 that the new variant could be up to 70% more transmissible than previous variants, although there was "considerable uncertainty". The French government said, two days later, that increased transmissibility had "not been clearly established". Vivek Murthy—who is a former U.S. Surgeon General, current nominee for Surgeon General, and co-chair of the US COVID-19 Advisory Board—agreed that the variant seemed to be more easily transmissible.

Misconceptions

$R_0$ is the reproduction number without immunity and social distancing measures; $R_t$ is the reproduction number at the level of immunity and social distancing at a time $t$ (e.g., the current time). It has been reported that the variant has an elevated current $R_t$, and values for the difference have been estimated. $R_0$ is important for the level of immunity required to start relieving social distancing measures while avoiding exponential growth. The variant also has an elevated $R_0$ but the (likely higher) differences have not been reported.

The modelling used by Eric Volz et al and Grabowky et al works with just an enhanced transmissibility factor, the relative reproduction number, as a "multiplicative advantage" of 1.74 to the reproduction number $R_t$. In their modeling, the relative growth and thus the moment the variant becomes dominant does not depend on social distancing measures or traveling restrictions.

Virulence

NERVTAG concluded on 18 December 2020 that there were insufficient data to reach a conclusion regarding disease severity. At 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."

On 23 December NERVTAG member Wendy Barclay said in an interview that there was no evidence that "long covid" was related to a variant, saying that it was most probably due to a difference in individuals' host response.

Public Health England's laboratory at Porton Down was running tests to find evidence whether the new variant affects the severity of disease.

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 glycoprotein (VOC-202012/01 has a change, 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 glycoprotein—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 more mutations occur, the vaccines may 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 in many countries are said to be likely undetected as most tests do not distinguish between this variant and other COVID-19 variants, and many COVID-19 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.

As of 20 December 2020, nine cases of the new variant had been reported in Denmark, four in Belgium and one each in 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 new variant, equalling an overall frequency of less than 1% of the sampled cases in the period from its first detection in the country in mid-November to the end of December, but showing a slowly rising tendency. Luxembourg and Vietnam reported their first case of this variant on 2 January 2021. Cyprus announced on 3 January 2021 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. 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 the US state of Georgia reported their first case of VOC-202012/01, with the person infected in Georgia having no travel history. 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. Mexico and Russia reported their first case of this variant on 10 January, then Malaysia on 11 January. The Philippines detected the presence of the variant on 13 January.

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 January 16, 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 change

A variant with the same N501Y change (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 change 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 were required 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.

See also

• Variants of SARS-CoV-2

References

Explanatory notes

Sources

External links

• "UK reports new variant, termed VUI 202012/01". GISAID.
• "Threat Assessment Brief 20 December 2020 — "Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom. European Centre for Disease Prevention and Control.