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SARS-CoV-2 Alpha variant

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The first Variant Under Investigation in December 2020 (VUI – 202012/01),[1][a] also known as lineage B.1.1.7,[4][5] is a variant of SARS-CoV-2, the virus that causes COVID-19. The variant was first detected in the United Kingdom in October 2020 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 England; this increase is thought to be at least partly because of mutation N501Y inside the spike glycoprotein's receptor-binding domain, which is needed for binding to ACE2 in human cells.

Genetics

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 Consortium (COG-UK).[7] 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.[8]

The VUI – 202012/01 variant is defined by 17 mutations.[b] One of the most important mutations seems to be N501Y,[7] a change from asparagine (N) to tyrosine (Y) in amino-acid site 501.[9] This is because of its position inside the spike glycoprotein's receptor-binding domain (RBD), which binds to human and murine ACE2.[4] Mutations in the RBD can change antibody recognition and ACE2 binding specificity[10] and lead to the virus becoming more infectious;[7] indeed, N501Y has been shown to enhance ACE2 binding affinity.[11] Furthermore, 69–70del, a deletion of the amino acids in positions 69 and 70 of the spike glycoprotein, has been discovered "in viruses that eluded the immune response in some immunocompromised patients".[12]

At a telecon meeting on 18 December, the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), which advises the UK government, considered the possibility of antigenic escape, saying: "The location of the mutations in the receptor-binding domain of the spike glycoprotein raises the possibility that this variant is antigenically distinct from prior variants. Four probable reinfections have been identified amongst 915 subjects with this variant, but further work is needed to compare this reinfection rate with comparable data sets."[13]

Detection

VUI-202012/01 was discovered in October 2020 by the COVID-19 Genomics UK (COG-UK) consortium from a sample taken in September the same year.[6]

Characteristics

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]

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".[14][15] The French government disputed Johnson's opinion, saying that "has not been demonstrated at this stage".[16] 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 with Johnson that the variant seemed to be more easily transmissible.[17][18]

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;[14][15] Vivek Murthy agreed with this.[18]

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."[7]

As of 19 December 2020 Public Health England's laboratory at Porton Down was running tests to find evidence whether the new variant affects the severity of disease.[19]

Genetic sequencing of this strain has shown a Q27stop mutation which "truncates the ORF8 protein or renders it inactive".[20]

A previous study reported that "SARS-CoV-2 variants isolated in the beginning of the coronavirus disease 2019 (Covid-19) pandemic that were deleted of the ORF8 gene have been associated to milder symptoms and better disease outcome", "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."[21]

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 targeted by the three leading vaccines, 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.[7]

However, as more mutations occur, the vaccines may need to be altered. SARS-CoV-2 does not mutate as quickly as influenza viruses, and the new vaccines that had proved effective by the end of 2020 are types that can be adjusted if necessary.[22] 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 VUI – 202012/01 strain as against previous strains.[16][23]

As of 20 December 2020 Public Health England confirmed there is "no evidence" to suggest that the new strain would be resistant to the Pfizer–BioNTech vaccine currently being used in the UK's vaccination programme, and that people should still be protected.[24]

Spread

The first case was likely in mid-September in London or Kent, United Kingdom.[25] 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.[19] 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.[14][26] Later on the same day it was reported that four had been found in Belgium,[27] and one in Italy.[28] The United Kingdom and Denmark are sequencing their coronavirus cases at considerably higher rates than most others,[29] and it was considered likely that additional countries would detect the variant later.[30] A strain with the same N501Y mutation (which could result in higher transmissibility), but separate lineage from the UK strain, was also detected in South Africa.[31] The N501Y mutation 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.[32]

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 VUI – 202012/01—effective from 20 December 2020.[33][34] During December 2020, an increasing number of countries around the world either announced temporary bans, or were considering banning, passenger travel from the UK, and in several cases from other countries such as the Netherlands and Denmark. 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.[35][36] 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.[37][17][38][39][40]As of 21 December 2020 the only continent bar Antarctica with no bans on travel from the UK was Australia, confident that their 14-day quarantine on all arrivals was sufficient.[41]

See also

  • Cluster 5, a variant of SARS-CoV-2 found in Danish mink farms with another mutation in the receptor-binding domain
  • 501.V2 Variant, a variant of SARS-CoV-2 found in South Africa with mutations that partially resemble VUI – 202012/01

References

Explanatory notes
  1. ^ Written as VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01) by GISAID[2] and the ECDC.[3]
  2. ^ List of mutations, adapted from COG-UK (2020), Table 1b:
    • In the ORF1ab: T1001I, A1708D, I2230T, SGF 3675–3677
    • In the spike: 69–70del, Y144del, N501Y, A570D, P681H, T716I, S982A, D1118H
    • In the ORF8: Q27stop, R52I, Y73C
    • In the N terminal: D3L, S235F
Sources
  1. ^ "PHE investigating a novel strain of COVID-19". Public Health England. 14 December 2020.
  2. ^ "UK reports new variant, termed VUI 202012/01". GISAID. Retrieved 20 December 2020.
  3. ^ "Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom -Threat Assessment Brief" (PDF). European Centre for Disease Prevention and Control (ECDC). 20 December 2020.
  4. ^ a b Andrew Rambaut et al. on behalf of COVID-19 Genomics Consortium UK (2020). Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations (Report). Retrieved 20 December 2020.{{cite report}}: CS1 maint: numeric names: authors list (link)
  5. ^ Kupferschmidt, Kai; 2020 (20 December 2020). "Mutant coronavirus in the United Kingdom sets off alarms but its importance remains unclear". Science | AAAS. Retrieved 21 December 2020. {{cite web}}: |last2= has numeric name (help)CS1 maint: url-status (link)
  6. ^ a b "Covid: Ireland, Italy, Belgium and Netherlands ban flights from UK". BBC News. 20 December 2020.
  7. ^ a b c d e Wise, Jacqui (16 December 2020). "Covid-19: New coronavirus variant is identified in UK". BMJ. 371. doi:10.1136/bmj.m4857. ISSN 1756-1833. PMID 33328153.
  8. ^ "Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus". Cell. 182 (4): 812–827.e19. 20 August 2020. doi:10.1016/j.cell.2020.06.043 – via ScienceDirect.
  9. ^ 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.
  10. ^ COG-UK (2020), p. 1.
  11. ^ COG-UK (2020), p. 4; Table 1b.
  12. ^ Kupferschmidt, Kai (20 December 2020). "Mutant coronavirus in the United Kingdom sets off alarms, but its importance remains unclear".
    See also COG-UK (2020), p. 4: "69-70del has been identified in variants associated with immune escape in immunocompromised patients [...]".
  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. ^ a b c "Covid: WHO in 'close contact' with UK over new virus variant". BBC News. 20 December 2020.
  15. ^ a b "As it happened: Stricter Covid rules for Christmas outlined". BBC News. 19 December 2020.
  16. ^ a b "Covid vaccines 'still effective' against fast-spreading mutant strain". Metro. 20 December 2020.
  17. ^ a b GRIESHABER, KIRSTEN; HUI, SYLVIA (21 December 2020). "More EU nations ban travel from UK, fearing virus variant". AP NEWS.
  18. ^ 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.
  19. ^ a b "COVID-19 Genomics UK (COG-UK) Consortium - Wellcome Sanger Institute". www.sanger.ac.uk. Retrieved 19 December 2020.
  20. ^ "Preliminary genomic characterization of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations". virological.org. Retrieved 21 December 2020.
  21. ^ "Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2". www.sciencedirect.com. Retrieved 21 December 2020.
  22. ^ 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.
  23. ^ "Vaccines effective against new virus strain – German health minister". INQUIRER.net. AFP. 21 December 2020.
  24. ^ "COVID-19 (SARS-CoV-2): information about the new virus variant". Gov.uk. Public Health England. 20 December 2020. Retrieved 21 December 2020.
  25. ^ 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.
  26. ^ 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.
  27. ^ Alan Hope (20 December 2020). "Netherlands bans flights from UK over new Covid mutation". The Brussels Times.
  28. ^ "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.
  29. ^ Knudsen, T.H. (20 December 2020). "Dansk Oxford-professor: Danmark skal gøre alt for, at ny virusvariant ikke spreder sig". DR (in Danish).
  30. ^ Mandavilli, Apoorva; Landler, Mark; Castle, Stephen (20 December 2020). "Scientists urge calm about coronavirus mutations, which are not unexpected". New York Times.
  31. ^ "Mutant coronavirus in the United Kingdom sets off alarms but its importance remains unclear". Science Mag. 20 December 2020.
  32. ^ "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)
  33. ^ "Covid-19: Christmas rules tightened for England, Scotland and Wales". BBC News. 20 December 2020. Retrieved 20 December 2020.
  34. ^ Fairnie, Robert (19 December 2020). "Travel between Scotland and rest of UK banned over Christmas as border is closed". edinburghlive. Retrieved 20 December 2020.
  35. ^ 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.
  36. ^ Michaels, Daniel (20 December 2020). "Countries Ban Travel From U.K. in Race to Block New Covid-19 Strain". WSJ.
  37. ^ 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)
  38. ^ 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.
  39. ^ "Covid-19: UK isolation grows as more countries ban travel". BBC News. 21 December 2020.
  40. ^ "Morocco bans air travel with UK over new virus". Reuters. 20 December 2020.
  41. ^ Davey, Melissa (21 December 2020). "Australian health officials cast doubt on claim new UK Covid strain more infectious". The Guardian. Minister Greg Hunt says Australia will not ban flights from UK because it has mandatory 14-day hotel quarantine

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