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SARS-CoV-2 Alpha variant

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Variant of Concern 202012/01 (VOC-202012/01),[1] previously known as the first Variant Under Investigation in December 2020 (VUI – 202012/01)[2][a][b] and also as lineage B.1.1.7,[3][4] is a variant of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).[5] The variant was first detected in October 2020 during the COVID-19 pandemic in the United Kingdom from a sample taken the previous month,[6] 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 inside the spike glycoprotein's receptor-binding domain, which is needed for binding to ACE2 in human cells.

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.[7]

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.[3] 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.[3]

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 came to light 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.[8]

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.[9][7]

Characteristics

Genetics

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. (2020), 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.[10] The focus on mutations is a common way to track the spread of the virus. As well as showing, for example, that SARS-CoV-2 arrived in the UK from over 1,000 separate incidents, it also shows that a variant with the mutation G614 has completely replaced the previous D614.[11]

The VOC-202012/01 variant is defined by 23 mutations: 13 non-synonymous mutations, 4 deletions, and 6 synonymous mutations[12] (i.e., there are 17 mutations that change proteins and six that do not[7]).

Contagiousness

NERVTAG concluded at a telecon meeting 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.[13] Data seen by NERVTAG included a genomic analysis showing that this particular lineage was growing around 70% faster. They also found a correlation between higher reproduction rate and detection of lineage B.1.1.7. While there may be other explanations, it is likely that this variant is more transmissible; laboratory studies will clarify this.[7]

One of the most important changes in VOC-202012/01 seems to be N501Y,[10] a change from asparagine (N) to tyrosine (Y) at amino-acid site 501.[14] This is because of its position inside the spike glycoprotein's receptor-binding domain (RBD)—more specifically inside the receptor-binding motif (RBM),[15] a part of the RBD[16]—which is used to bind to human ACE2.[17] Mutations in the RBD can change antibody recognition and ACE2 binding specificity.[17] Furthermore, it can lead to the virus becoming more infectious;[10] indeed, in a report published by Public Health England on 21 December 2020, 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".[18]

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".[19][20] The French government disputed Johnson's opinion, saying that "has not been demonstrated at this stage".[21] Vivek Murthy, who is a former U.S. Surgeon General, current nominee for Surgeon General, and co-chair of the COVID-19 Advisory Board, agreed that the variant seemed to be more easily transmissible.[22][23]

Virulence

NERVTAG had concluded at a meeting 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;[19][20] Vivek Murthy agreed with this.[23]

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."[10]

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.[24]

Public Health England's laboratory at Porton Down was running tests to find evidence whether the new variant affects the severity of disease.[25]

Genetic sequencing of VOC-202012/01 has shown a Q27stop mutation which "truncates the ORF8 protein or renders it inactive".[3] 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".[26] 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".[26]

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",[27] and has also been been found "in association with other RBD changes".[18]

Vaccine effectiveness

As of late 2020 several COVID-19 vaccines were being deployed or under development. While the new variant has mutations to the spike glycoprotein, which is targeted by the three leading vaccines,[which?] the immune system produces antibodies to several regions of the protein in response to the vaccine, so it is thought to be unlikely that a single mutation would make the vaccines less effective.[10]

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.[28] 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 strain as against previous variants.[21][29]

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.[8]

At an 18 December meeting, NERVTAG came to the conclusion "that there are currently insufficient data to draw any conclusion on [...] [a]ntigenic escape".[13]

Spread

The first case was likely in mid-September 2020 in London or Kent, United Kingdom.[30] 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.[25] 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.[31] In mid-December, it was estimated that almost 60 percent of cases in London involved VOC-202012/01.[32] On 20 December 2020, the BBC reported that the World Health Organization (WHO) had said that nine cases of the new variant had been reported in Denmark, and one each in the Netherlands and Australia.[19][33] Later on the same day it was reported that four had been found in Belgium,[34] and one in Italy.[35] The United Kingdom and Denmark are sequencing their SARS-CoV-2 cases at considerably higher rates than most others,[36] and it was considered likely that additional countries would detect the variant later.[37]

A variant with the same N501Y change (which may result in higher transmissibility), but separate lineage from the UK strain, was also detected in South Africa.[38] 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.[39]

Control

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.[40][41] 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.[42] 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.[43][44]

Many countries around the world imposed restrictions on passenger travel from the United Kingdom; neighbouring France also restricted manned goods vehicles. Some also applied restrictions on travel from other countries.[45][22][46][47] As of 21 December 2020, at least 42 countries had restricted flights from the UK.[42]

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

References

Explanatory notes
  1. ^ Written as VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) by GISAID[48] and the ECDC.[49]
  2. ^ The nomenclature is explained by Chand et al. (2020), p. 2:

    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.
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. ^ "PHE investigating a novel strain of COVID-19". Public Health England. 14 December 2020.
  3. ^ a b c d Rambaut, Andrew; Loman, Nick; Pybus, Oliver; Barclay, Wendy; Barrett, Jeff; Carabelli, Alesandro; Connor, Tom; Peacock, Tom; L. Robertson, David; Vol, Erik (2020). Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations (Report). Written on behalf of COVID-19 Genomics Consortium UK. Retrieved 20 December 2020.{{cite report}}: CS1 maint: multiple names: authors list (link)
  4. ^ Kupferschmidt, Kai (20 December 2020). "Mutant coronavirus in the United Kingdom sets off alarms but its importance remains unclear". Science Mag. Retrieved 21 December 2020.{{cite web}}: CS1 maint: ref duplicates default (link) CS1 maint: url-status (link)
  5. ^ 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.
  6. ^ "Covid: Ireland, Italy, Belgium and Netherlands ban flights from UK". BBC News. 20 December 2020.
  7. ^ a b c d Peacock, Sharon (22 December 2020). "Here's what we know about the new variant of coronavirus". The Guardian.
  8. ^ a b "COVID-19 (SARS-CoV-2): information about the new virus variant". Gov.uk. Public Health England. 20 December 2020. Retrieved 21 December 2020.
  9. ^ "New coronavirus variant: What do we know?". BBC. Retrieved 22 December 2020.
  10. ^ a b c d e Wise, Jacqui (16 December 2020). "Covid-19: New coronavirus variant is identified in UK". The BMJ. 371. doi:10.1136/bmj.m4857. ISSN 1756-1833. PMID 33328153. S2CID 229291003.
  11. ^ Korber, Bette; Fischer, Will M.; Gnanakaran, Sandrasegaram; Yoon, Hyejin; Theiler, James; Abfalterer, Werner; Hengartner, Nick; Giorgi, Elena E.; Bhattacharya, Tanmoy; Foley, Brian; Hastie, Kathryn M.; Parker, Matthew D.; Partridge, David G.; Evans, Cariad M.; Freeman, Timothy M.; De Silva, Thushan I.; McDanal, Charlene; Perez, Lautaro G.; Tang, Haili; Moon-Walker, Alex; Whelan, Sean P.; Labranche, Celia C.; Saphire, Erica O.; Montefiori, David C.; Angyal, Adrienne; Brown, Rebecca L.; Carrilero, Laura; Green, Luke R.; Groves, Danielle C.; et al. (20 August 2020). "Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus". Cell. 182 (4): 812–827.e19. doi:10.1016/j.cell.2020.06.043. PMC 7332439. PMID 32697968 – via ScienceDirect.
  12. ^ Chand et al. (2020), p. 5.
  13. ^ 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".
  14. ^ COG-UK update on SARS-CoV-2 Spike mutations of special interest | Report 1 (PDF) (Report). COVID-19 Genomics UK Consortium (COG-UK). 19 December 2020. p. 7.
  15. ^ COG-UK (2020), p. 4.
  16. ^ Yi, C.; Sun, X.; Ye, J.; et al. (2020). "Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies". Cellular & Molecular Immunology. 17: 621–630. doi:10.1038/s41423-020-0458-z. "
  17. ^ a b COG-UK (2020), p. 1.
  18. ^ a b Chand et al. (2020), p. 6.
  19. ^ a b c "Covid: WHO in 'close contact' with UK over new virus variant". BBC News. 20 December 2020.
  20. ^ a b "As it happened: Stricter Covid rules for Christmas outlined". BBC News. 19 December 2020.
  21. ^ a b "Covid vaccines 'still effective' against fast-spreading mutant strain". Metro. 20 December 2020.
  22. ^ a b GRIESHABER, KIRSTEN; HUI, SYLVIA (21 December 2020). "More EU nations ban travel from UK, fearing virus variant". AP NEWS.
  23. ^ a b Berger, Miriam (20 December 2020). "Countries across Europe halt flights from Britain over concerns about coronavirus mutation". Washington Post. ISSN 0190-8286. Archived from the original on 20 December 2020. Retrieved 20 December 2020.
  24. ^ Badshah, Nadeem (23 December 2020). "Coronavirus live news: new variant already in 'great majority if not all' European countries, says expert". The Guardian.
  25. ^ a b "COVID-19 Genomics UK (COG-UK) Consortium - Wellcome Sanger Institute". www.sanger.ac.uk. Retrieved 23 December 2020.
  26. ^ a b Zinzula, Luca (2020). "Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2". Biochemical and Biophysical Research Communications. doi:10.1016/j.bbrc.2020.10.045. PMC 7577707. Retrieved 21 December 2020.
  27. ^ Kupferschmidt (2020). See also COG-UK (2020), p. 4: "69-70del has been identified in variants associated with immune escape in immunocompromised patients [...]."
  28. ^ Patel-Carstairs, Sunita (19 December 2020). "COVID-19: London and South East set for Tier 4 rules - as new COVID variant 'real cause for concern'". Sky News.
  29. ^ "Vaccines effective against new virus strain – German health minister". INQUIRER.net. AFP. 21 December 2020.
  30. ^ Higgins-Dunn, N. (19 December 2020). "The U.K. has identified a new Covid-19 strain that spreads more quickly. Here's what they know". MSNBC.
  31. ^ Gallagher, James (20 December 2020). "New coronavirus variant: What do we know?". BBC News. Retrieved 21 December 2020.
  32. ^ Ross, T.; Spence, E. (19 December 2020). "London Begins Emergency Lockdown as U.K. Fights New Virus Strain". Bloomberg News.
  33. ^ Henley, Jon; Jones, Sam; Giuffrida, Angela; Holmes, Oliver (20 December 2020). "EU to hold crisis talks as countries block travel from UK over new Covid strain". The Guardian.
  34. ^ Alan Hope (20 December 2020). "Netherlands bans flights from UK over new Covid mutation". The Brussels Times.
  35. ^ "Coronavirus, in Italia un soggetto positivo alla variante inglese" [Coronavirus, one person tests positive in Italy for the English variant]. la Repubblica (in Italian). 20 December 2020.
  36. ^ Knudsen, T.H. (20 December 2020). "Dansk Oxford-professor: Danmark skal gøre alt for, at ny virusvariant ikke spreder sig" (in Danish). DR.
    See also: "Global sequencing coverage". covidcg.org. Retrieved 23 December 2020.
  37. ^ Mandavilli, Apoorva; Landler, Mark; Castle, Stephen (20 December 2020). "Scientists urge calm about coronavirus mutations, which are not unexpected". New York Times.
  38. ^ Kupferschmidt (2020).
  39. ^ "Expert reaction new restrictions and the new SARS-CoV-2 variant". Science Media Centre. Retrieved 21 December 2020.{{cite web}}: CS1 maint: url-status (link)
  40. ^ "Covid-19: Christmas rules tightened for England, Scotland and Wales". BBC News. 20 December 2020. Retrieved 20 December 2020.
  41. ^ Fairnie, Robert (19 December 2020). "Travel between Scotland and rest of UK banned over Christmas as border is closed". edinburghlive. Retrieved 20 December 2020.
  42. ^ a b Halliday, Josh (21 December 2020). "Calls for national lockdown in England to curb spread of new Covid strain". The Guardian.
  43. ^ Henley, Jon; Jones, Sam; Giuffrida, Angela; Holmes, Oliver (20 December 2020). "EU to hold crisis talks as countries block travel from UK over new Covid strain". The Guardian.
  44. ^ Michaels, Daniel (20 December 2020). "Countries Ban Travel From U.K. in Race to Block New Covid-19 Strain". WSJ.
  45. ^ Berger, Miriam (20 December 2020). "Countries across Europe halt flights from Britain over concerns about coronavirus mutation". Washington Post. ISSN 0190-8286. Archived from the original on 20 December 2020. Retrieved 20 December 2020. {{cite news}}: |archive-date= / |archive-url= timestamp mismatch; 21 December 2020 suggested (help)
  46. ^ Quinn, Edna Mohamed(now) Ben; Davies (earlier), Caroline; Davidson, Helen; Wahlquist (earlier), Calla; Walker, Shaun (20 December 2020). "Cases of new strain reported outside of UK – as it happened". The Guardian. ISSN 0261-3077. Retrieved 21 December 2020.
  47. ^ "Covid-19: UK isolation grows as more countries ban travel". BBC News. 21 December 2020.
  48. ^ "UK reports new variant, termed VUI 202012/01". GISAID. Retrieved 20 December 2020.
  49. ^ Threat Assessment Brief: Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom (PDF) (Report). European Centre for Disease Prevention and Control (ECDC). 20 December 2020.
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