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Countries with confirmed cases of VOC-202012/01
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Variant of Concern 202012/01[1] (VOC-202012/01; also known as lineage B.1.1.7, see § Nomenclature) is a variant of SARS-CoV-2, the virus that causes COVID-19.[2] The variant was first detected in October 2020 during the COVID-19 pandemic in the United Kingdom from a sample taken the previous month,[3] and it quickly began to spread by mid-December. It is correlated with a significant increase in the rate of COVID-19 infection in 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 is needed for binding to ACE2 in human cells. The variant is also notable for the higher number of mutations it contains compared to the recorded trend to date.[4]

Nomenclature

The variant is known by multiple names. In government and media reports it is commonly[dubious – discuss] referred as UK COVID-19 variant[5][6][7][8] and UK coronavirus variant,[9][10][11] among other names. The variant had previously been named the first Variant Under Investigation in December 2020 (VUI – 202012/01) by Public Health England,[12][a] 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.[b] 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.[14]

Detection

The new variant was detected in early December 2020, combining genome data with knowledge that the rates of infection in Kent were not falling despite national restrictions.[4]

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.[14] 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.[14]

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.[15]

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.[16][4]

Characteristics

Genetics

Defining mutations in VOC-202012/01
(change of amino acid only)
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.[17]

The VOC-202012/01 variant is defined by 23 mutations: 13 non-synonymous mutations, 4 deletions, and 6 synonymous mutations[18] (i.e., there are 17 mutations that change proteins and six that do not[4]).

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.[19] Data seen by NERVTAG indicated that this variant has a "selection coefficient" of 0.70 (70%), presuming a generational interval of 6.5 days.[20][21] In later work, the relative reproduction number, which is the exponent of the selection coefficient, was used as a measure. (As a relevant example, ) Using slightly different data, the relative reproduction number ("multiplicative advantage") was determined to be 1.74, that is, that the variant is 74% more transmissible. The variant became the dominant strain in London, East of England and the South East from low levels in one to two months.[22] A surge of covid-19 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.[23][24] It requires tougher restrictions to avoid fast exponential growth of a virus which is this transmissible.[25]

One of the most important changes in VOC-202012/01 seems to be N501Y,[17] a change from asparagine (N) to tyrosine (Y) at amino-acid site 501.[26] This is because of its position inside the spike glycoprotein's receptor-binding domain (RBD)—more specifically inside the receptor-binding motif (RBM),[27] a part of the RBD[28]—which is used to bind to human ACE2.[29] Mutations in the RBD can change antibody recognition and ACE2 binding specificity.[29] Furthermore, it can lead to the virus becoming more infectious;[17] 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".[30]

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".[31][32] The French government disputed Johnson's opinion, saying that "has not been demonstrated at this stage".[33] 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.[34][35]

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;[31][32] Vivek Murthy agreed with this.[35]

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."[17]

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.[36]

Public Health England's laboratory at Porton Down was running tests to find evidence whether the new variant affects the severity of disease.[37]

Genetic sequencing of VOC-202012/01 has shown a Q27stop mutation which "truncates the ORF8 protein or renders it inactive".[14] An earlier study of SARS-CoV-2 variants deleted of the ORF8 gene noted that they "have been associated to milder symptoms and better disease outcome".[38] 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".[38]

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",[39]</ref> and has also been found "in association with other RBD changes".[30]

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 COVID-19 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 identify the new strain. However, Public Health England determined that rapid tests evaluated and used in the United Kingdom detect VOC-202012/01.[40]

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.[41] 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.[33][42]

On 18 December, NERVTAG came to the conclusion "that there are currently insufficient data to draw any conclusion on [...] [a]ntigenic escape".[19]

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.[15]

Spread

The first case was likely in mid-September 2020 in London or Kent, United Kingdom.[43] 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.[37] 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.[44] In mid-December, it was estimated that almost 60 percent of cases in London involved VOC-202012/01.[45]

As of 20 December 2020, nine cases of the new variant had been reported in Denmark,[31][46] four in Belgium[47] and one each in the Netherlands, Australia[31][46] and Italy.[48] Shortly after, it was reported that it also had been found in Iceland and Gibraltar.[49][50] Singapore, Israel and Northern Ireland reported their first cases on 23 December.[51][52][53] Germany and Switzerland confirmed their first cases on 24 December,[54][55] and the Republic of Ireland and Japan confirmed their first cases on 25 December.[56][57]

The first cases in Canada, France, Lebanon, Spain and Sweden were reported on 26 December.[58][59][60][61] Jordan, Norway, and Portugal reported their first case on 27 December,[62][63] Finland and South Korea reported their first cases on 28 December,[64][65] and Chile, India, Pakistan and the United Arab Emirates reported their first cases on 29 December.[66][67][68][69] The first case of new variant in Malta and Taiwan are reported on 30 December.[70][71] China and Brazil reported their first cases of the new variant on 31 December.[72][73] The United Kingdom and Denmark are sequencing their SARS-CoV-2 cases at considerably higher rates than most others,[74] and it was considered likely that additional countries would detect the variant later.[75]

The United States reported a case in Colorado with no travel history on 29 December.[76] This was followed by the discovery of three additional cases in California, Florida, and New York on 30 and 31 December, and 4 January 2021, respectively.[77][78][79] 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 still required for detection of this variant.[80] Turkey detected its first cases in 15 people from England on 1 January 2021.[81] 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.[82][83] Luxembourg and Vietnam reported their first case of this variant on 2 January 2021.[84][85] Cyprus announced on 3 January 2021 that it had detected VOC-202012/01 in 12 samples.[86] 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,[87] and the latter reported the cases from a family of four who had arrived from Kent.[88]

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 also detected in South Africa.[39] The N501Y change has also been detected elsewhere: in Australia in June–July, in the US in July, and in Brazil in April, and it is not yet clear if it arose spontaneously in the UK, or was imported.[89]

Control

In the presence of an extra infectious variant, stronger social distancing and lockdown were required to avoid overwhelming the population due to its tendency to grow exponentially.[90]

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.[91][92] 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.[93] 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.[94][95]

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).[96] Some also applied restrictions on travel from other countries.[34][97][98][99] As of 21 December 2020, at least 42 countries had restricted flights from the UK,[93] and Japan was restricting entry of all foreign nationals after cases of the new variant were detected in the country.[100]

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.[101][102]

See also

  • Cluster 5, a variant of SARS-CoV-2 found in Danish mink farms with another mutation in the receptor-binding domain, Y453F
  • 501.V2 variant, a variant of SARS-CoV-2 found in South Africa, also with N501Y along with two other changes in the receptor-binding domain
  • Variants of SARS-CoV-2

References

Explanatory notes
  1. ^ Written as VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) by GISAID[103] and the ECDC.[104]
  2. ^ This redesignation is explained in the report:

    SARS-COV-2 variants if considered to have concerning epidemiological, immunological or pathogenic properties are raised for formal investigation. At this point they are designated Variant Under Investigation (VUI) with a year, month, and number. Following risk assessment with the relevant expert committee, they are designated Variant of Concern (VOC). This variant was designated VUI-202012/01 on detection and on review re-designated as VOC-202012/01 on 18/12/20 and GISAID entry EPI_ISL_601443 was declared to be the canonical genome.[13]
Sources
  1. ^ Chand, Meera; Hopkins, Susan; Dabrera, Gavin; Achison, Christina; Barclay, Wendy; Ferguson, Neil; Volz, Erik; Loman, Nick; Rambaut, Andrew; Barrett, Jeff (21 December 2020). Investigation of novel SARS-COV-2 variant: Variant of Concern 202012/01 (PDF) (Report). Public Health England. Retrieved 22 December 2020.
  2. ^ Zimmer, Carel; Carey, Benedict (21 December 2020). "The U.K. Coronavirus Variant: What We Know = A newly identified variant of the SARS-CoV-2 virus appears to be more contagious than established ones. Here's what scientists know". The New York Times. Retrieved 23 December 2020.
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  4. ^ a b c d Peacock, Sharon (22 December 2020). "Here's what we know about the new variant of coronavirus". The Guardian.
  5. ^ "Vietnam proposes suspending all flights from countries with UK COVID-19 variant". Reuters. 4 January 2021.
  6. ^ "More Contagious Variant Of COVID-19 Reaches Florida". NBC Miami and Florida Department of Health. 1 January 2021. Florida has evidence of the first identified case of the UK COVID-19 variant in Martin County. The individual is a male in his 20s with no history of travel. The Department is working with the CDC on this investigation. {{cite news}}: Check |archiveurl= value (help)
  7. ^ "Ontario identifies 1st cases of COVID-19 variant detected in the U.K." Canadian Broadcasting Corporation. 27 December 2020.
  8. ^ "Joint statement on first COVID-19 U.K. variant case in B.C." Government of British Columbia press release. 27 December 2020.
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  13. ^ Chand et al., p. 2.
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  19. ^ a b New and Emerging Respiratory Virus Threats Advisory Group (18 December 2020). "NERVTAG meeting on SARS-CoV-2 variant under investigation: VUI-202012/01".
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  27. ^ COG-UK, p. 4.
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    See also COG-UK, p. 4: "69-70del has been identified in variants associated with immune escape in immunocompromised patients [...]."
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    See also: "Global sequencing coverage". covidcg.org. Retrieved 23 December 2020.
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Scholia has a profile for SARS-CoV-2 Alpha variant (Q104376647).
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