Cluster 5 Explained

Cluster 5 is a designation used by the Danish Statens Serum Institut for a virus variant described by the institute in autumn 2020, in connection with investigations of SARS-CoV-2 infection among mink and humans in the north of Jutland, Denmark.[1]

On 3 November 2020, the institute delivered a risk assessment, in which a preliminary experiment with this virus variant described on one and a half pages,[2] was the basis for an assessment concerning the efficacy of future COVID-19 vaccines.[3] With reference to this risk assessment, the Danish government on 4 November 2020 mandated the killing all the country's mink.[4] and a lockdown with tightened restrictions was introduced in seven North Jutland municipalities.

At the time the decision to kill all Danish mink was made, the virus variant had last been detected on 15 September 2020.[5] [6] After subsequent testing and sequencing of positive samples in the seven North Jutland municipalities, the date of the latest finding was still 15 September 2020.[7] The World Health Organization wrote on 6 November 2020 with reference to the preliminary experiment, that "Further scientific and laboratory-based studies are required to verify preliminary findings reported and to understand any potential implications of this finding in terms of diagnostics, therapeutics and vaccines in development."[8]

The Danish Medicines Agency was asked for its assessment of the virus variant, the day after the government had decided to kill all the country's mink.[9] The agency concludes in its assessment that the mutations that characterize the virus variant are not likely to have substantial impact on the efficacy of first-generation vaccines.[10]

Background

In 2019, Denmark was the largest producer of mink fur in the world,[11] with the vast majority of the Danish farms located in northern and western Jutland.[12] In recent years the industry had generally been in decline in the country.[13] Along with bats, pangolins, and humans, minks are one of the many mammal species that can be infected with coronaviruses.[14]

Although the role of pangolins in the spread of COVID-19 was gradually being dismissed by scientists,[15] [16] several articles claimed that Chinese mink farms may have played a role in the emergence of COVID-19.[17] [18] [19] [20] [21] In partnership with science journalist Yves Sciama, they conducted an investigation for Reporterre between November and December 2020.[22] [23] [24] The day after, transmission of the virus from minks to humans, and mutations related to mink, were documented in the journal Science, which prompted the Dutch government to bring forward to the end of 2020 a ban on mink farming previously scheduled to go into effect in 2024.[25] After the discovery in the Netherlands, the authorities in Denmark initiated a large-scale surveillance program of all mink farms in the country, with regular testing and genomic sequencing.[26] The sequences of the Danish and Dutch mink-related viruses were deposited with the GISAID database.[27] The U.S. Department of Agriculture (USDA) confirmed that cases of minks ill with COVID-19 had been documented in Utah in August 2020.[28] Additional outbreaks have been detected in Michigan, Wisconsin, and Oregon.[29] As of 29 November 2020, COVID-19 infections in mink have been reported in Denmark, Italy, the Netherlands, Spain, Sweden, and the United States.[30] [31]

Classification

In Denmark, there have been five clusters of mink variants of SARS-CoV-2; the Danish State Serum Institute (SSI) has designated these as clusters 1–5 (Danish: Danish: cluster 1–5). In cluster 5, also referred to as ΔFVIspike by the SSI, several different mutations in the spike protein of the virus have been confirmed. The specific mutations include 69–70deltaHV (a deletion of the histidine and valine residues at the 69th and 70th position in the protein), Y453F (a change from tyrosine to phenylalanine at position 453, inside the spike protein's receptor-binding domain), I692V (isoleucine to valine at position 692), M1229I (methionine to isoleucine at position 1229), and a non-conservative substitution S1147L.[32] [33]

Mink-related mutations that partially resemble the mutations discovered in Denmark, although part of a separate genomic group, are known from the Netherlands.[34]

Implications for human health

On 5 November, BBC News reported that 12 cases of human infection with the cluster 5 variant had been detected.[35] A week later, an ECDC rapid risk assessment report indicated that 214 mink-related human cases had occurred, however, few of these, if any, are believed to have been additional cases related to the Cluster 5 outbreak.[36] By 20 November, no further human cases of the Cluster 5 strain were being detected despite widespread genetic sequencing which revealed 750 cases related to mink, and it was assessed that the Cluster 5 variant was no longer circulating in humans.[37]

History

Discovery

By 2 November 2020, the Danish state-owned independent research institute Statens Serum Institut (SSI) detected mutated variants of SARS-CoV-2 that could infect humans and could have dangerous effects in mink farms; human infections were associated with 191 positive mink farms. They publicly reported this on 3 November, calling variants with a known association to three farms "Cluster 5".[3] On 4 November 2020, Prime Minister of Denmark Mette Frederiksen stated that a mutated coronavirus was being transmitted to humans via minks, tied primarily to mink farms in North Jutland. A report by the SSI found that there had been 12 human infections (8 directly associated with mink farms, 4 in the nearby community) involving this mutation in Northern Jutland (being referred to as "cluster 5"), and its Antibody response was weaker. While the institute stated that the mutation appeared to be no more dangerous than other coronaviruses by itself, Kåre Mølbak and Tyra Grove Krause of the SSI warned that the mutation potentially could reduce the effect of COVID-19 vaccines currently under development, although it was unlikely to render them useless.[1] [38] [39] Furthermore, the weaker antibody response was shown to reduce immunity acquired by a prior infection.[3] SSI noted that while cluster 5 was of some concern, they were also worried about potential future mutations that could appear in mink, leading to their recommendation of closing down all the farms in the country.[40]

Lockdown and culling

As a preventative measure, Frederiksen announced that the country was already in the process of culling its mink population of about 14 million (initial reports of 15–17 million were based on estimates from earlier years when the industry was larger).[41] [42] To prevent spread of the mutation, it was also announced on 5 November that a lockdown and movement restrictions would be implemented in the North Jutland municipalities of Brønderslev, Frederikshavn, Hjørring, Jammerbugt, Læsø, Thisted, and Vesthimmerland effective 6 November,[43] All cultural institutions, cinemas, theatres, sports and leisure facilities, and dine-in restaurants were ordered closed, and travel into or out of the municipalities was prohibited. Public transport was suspended 9 November.[44] [45] Mass-testing was initiated (Denmark already had one of the world's highest test rates) and trace programs were further upscaled. The restrictions in Northern Jutland were initially planned to last until 3 December, but they could be reversed earlier depending on the speed of the mink culling and mass-testing of people, and if no new cases of cluster 5 were located.[46]

The WHO released a statement on the SARS-CoV-2 variants on 6 November. It explained that this cluster had a combination of mutations that had not been previously observed. The variant had moderately decreased sensitivity to neutralizing antibodies, but further studies would be required to understand implications regarding diagnostics, therapeutics and vaccines.[8] This was later echoed in a risk assessment published by the European Centre for Disease Prevention and Control (ECDC), which notes that the risk for the mink-related variants is similar to the general COVID-19 risk, but could be reassessed if the concerns raised regarding immunity, reinfection, vaccination, and treatment are confirmed when it comes to cluster 5 in particular, also noting that virus circulation in mink farms could pose other issues in the future, and providing guidelines for managing the risk.[47] [48] In late November, more than 10 million had been culled.[49]

International reactions

On 6 November, the United Kingdom announced that Denmark would be removed from the "corridor" whitelist of countries from which travellers may return without self-isolating for 14 days, citing the cluster-5 variant.[50] On 7 November, the United Kingdom announced that it would also prohibit entry by non-residents travelling from Denmark, and non-residents who had been to Denmark within the past 14 days. British citizens were still allowed to return home, but they, as well as all other members of their household, were required to self-isolate for 14 days. This travel ban was to be reviewed after a week.[51] [52] The restrictions were eventually lifted on 28 November.[53]

Aftermath

Following mass-testing, SSI announced on 19 November 2020 that they had found no new cases of cluster 5 and it was in all probability extinct. The special restrictions placed on some North Jutland municipalities were lifted on 19–20 November (they are still subjected to the standard COVID-19 restrictions that cover the entire country and are unrelated to the mink mutations).[7]

Political consequences

It was revealed in late November that the Minister for Agriculture, Mogens Jensen, and five other ministers had been made aware in September that the culling of the entire country's mink population, rather than just those in the infected areas, would be illegal. Facing calls for resignation from the parliamentary opposition and sharp public criticism,[54] Prime Minister Frederiksen acknowledged that the order to cull all minks was illegal, and Jensen resigned on 18 November.[55] A deal was later reached to retroactively make the government's order legal.[56] On 21 December 2020, in the Parliament of Denmark, the government and parliament's left wing parties passed a bill outlawing all mink production throughout 2021.[57] The bill does not contain provisions to remove legal responsibility for the previous culling but does retroactively legalize a bonus payout for swifter cullings.[57] The opposition parties (V, C, O, NB, LA) opposed.[58] On 25 January 2021,[59] a majority in the Danish parliament reached an agreement to compensate Danish mink farmers and others making a living off of mink farming for between 15.6 billion and 18.8 DKK[60] (2.1 billion EUR – 2.5 billion EUR).

See also

Notes and References

  1. Web site: Tyra Grove Krause . Mutationer i minkvirus . Mutations in mink virus . 5 Nov 2020 . Statens Serum Institut.
  2. Web site: Assessing cross-neutralization activity for SARS-CoV-2 spike mutants . . 2 Nov 2020.
  3. Web site: MFVM har anmodet SUM om en risikovurdering ift. human sundhed, hvis minkavlere efter aflivning af smittede dyr eller pelsning i 2020-sæsonen, fortsætter minkproduktionen ind i 2021 som normalt. Der er alene brug for en vurdering af risiko, ikke forslag til mulige løsninger. . MFVM has requested SUM for a risk assessment in relation to human health, if mink breeders, after killing infected animals or furring in the 2020 season, continue mink production into 2021 as normal. There is only a need for an assessment of risk, not proposals for possible solutions. . . 3 Nov 2020.
  4. News: Regeringen vil slå alle landets mink ned, men har endnu ikke lovgivningen på plads . The government wants to kill all the country's mink, but does not yet have the legislation in place . . Steffen Nyboe McGhie og Selin Türker . 8 Nov 2020.
  5. News: Allerede inden nedlukning af Nordjylland mente Kåre Mølbak, at cluster 5 kunne være »uddød« . Even before the lockdown of North Jutland, Kåre Mølbak believed that cluster 5 could be »extinct« . . Sebastian Abrahamsen . 18 Nov 2020.
  6. News: Minkmutation, der har ført til masseaflivninger og stor nedlukning, er med stor sandsynlighed allerede uddød: »Jeg vil vurdere, at den sagtens kan være forsvundet« . The mink mutation, which has led to mass culling and a major lockdown, is very likely already extinct: »I would assess that it could easily have disappeared« . Christian Birk, Flemming Pedersen og Philip Dam . 6 Nov 2020 . Berlingske.
  7. Web site: De fleste restriktioner lempes i Nordjylland . Most restrictions are relaxed in North Jutland . 19 Nov 2020 . Sundhedsministeriet.
  8. Web site: SARS-CoV-2 mink-associated variant strain – Denmark . https://web.archive.org/web/20201106224511/https://www.who.int/csr/don/06-november-2020-mink-associated-sars-cov2-denmark/en/ . dead . . 6 Nov 2020 . 6 Nov 2020.
  9. News: Detektor: Regeringen besluttede at aflive mink uden at spørge central myndighed . Detector: The government decided to kill mink without asking central authority . . Andreas Østergaard, Camilla Stampe, Sofie Frøkjær og Nikolaj Arve . 17 Nov 2020.
  10. Web site: Implications of mutations in the spike protein of Danish mink-de-rived SARS-CoV-2 isolates for vaccines and monoclonal antibody therapeutics. . . 9 Nov 2020.
  11. News: 4 November 2020. Denmark to cull up to 17m mink blamed for coronavirus mutation. Financial Times.
  12. Web site: Aflivninger rammer hårdt i minkland: – Jeg har mistet alt det, jeg har arbejdet på de sidste 33 år . Killings hit hard in minkland: – I have lost everything I have worked for the last 33 years . TV2. 5 November 2020.
  13. Web site: Fakta om minkbranchen i Danmark . Facts about the mink industry in Denmark. Danmark's Statistik. 5 November 2020.
  14. News: Huang. Pien. Dutch Minks Contract COVID-19 – And Appear To Infect Humans. All Things Considered. National Public Radio, Inc.. 25 June 2020. 3 October 2020.
  15. Web site: Covid-19 : le pangolin est-il vraiment responsable de l'épidémie? . Covid-19: is the pangolin really responsible for the epidemic? . Sciences et Avenir. 28 September 2020 . fr. 10 November 2020.
  16. Web site: COVID-19: time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans. ub.edu/. 17 September 2020.
  17. Web site: Origine du Sars-Cov2 : Vers une enquête à " rebrousse-poil " de l'OMS en Chine ? – par Yann Faure . Origin of Sars-Cov2: Towards an investigation against the grain of the WHO in China? – by Yann Faure . Yann. Faure . Les-crises.fr.
  18. Web site: Les élevages de visons ont un rôle dans la pandémie de Covid-19 . Mink farms have a role in the Covid-19 pandemic . Yann. Faure. reporterre.net. 10 November 2020.
  19. Web site: Les élevages de visons sont-ils la source du Covid en Europe? . Are mink farms the source of Covid in Europe? . Yves Sciama et Yann Faure. reporterre.net. 21 December 2020.
  20. Web site: Malgré les risques de Covid, les États rechignent à arrêter l'élevage de vison . Despite Covid Risks, States Are Reluctant To Stop Mink Farming . Yann. Faure. reporterre.net. 22 December 2020.
  21. Web site: Mounting evidence suggests mink farms in China could be the cradle of Covid-19. Yann Faure et Yves Sciama. reporterre.net. 8 January 2021.
  22. Web site: Covid-19 : et si le vison était le chaînon manquant? . Covid-19: what if mink was the missing link? . Emilie. Torgemen. Le Parisien. 9 January 2021 . 2 February 2021.
  23. Web site: Emergence du SARS-CoV-2: les soupçons sur les élevages d'animaux à fourrure s'accumulent . Emergence of SARS-CoV-2: the suspicions about the breeding of fur animals accumulate . AMÉLIE POINSSOT ET FRANÇOIS BOUGON. Mediapart. 18 January 2021.
  24. Web site: Covid-19 : le vison dans le viseur des chercheurs chinois . Covid-19: mink in the sights of Chinese researchers. Anne-Laure Barral. France Info. 12 January 2021.
  25. News: Not fur sale: COVID-19 brings Dutch mink farming to an end. The Economist. 5–11 September 2020.
  26. Web site: FAQ om overvågning og test i mink . FAQ on monitoring and testing in mink . Miljø- og Fødevareministeriet . 19 November 2020 . 27 November 2020 . https://web.archive.org/web/20201127115640/https://www.foedevarestyrelsen.dk/Dyr/Dyr-og-Covid-19/Mink-og-COVID-19/Sider/overvaagning-og-test-af-mink.aspx . dead .
  27. Web site: European Centre for Disease Prevention and Control . Detection of new SARS-CoV-2 variants related to mink . European Centre for Disease Prevention and Control . ECDC . 12 September 2021 . 3 . English . 12 November 2020.
  28. News: Cahan. Eli. 18 August 2020. COVID-19 hits U.S. mink farms after ripping through Europe. Science. American Association for the Advancement of Science. 3 October 2020.
  29. Web site: Alaa. Elassar. An Oregon mink farm has reported a Covid-19 outbreak. 29 November 2020 . 29 November 2020. CNN.
  30. News: 8 November 2020. 6 countries find coronavirus at mink farms; fears mutation could hinder vaccine. The Times of Israel. 9 November 2020. Italy, the Netherlands, Spain and Sweden are the other nations to have discovered SARS-CoV-2 in minks, WHO said in a statement..
  31. News: 9 November 2020. Israelis may be infected with new coronavirus strain from Denmark minks. The Jerusalem Post. 9 November 2020. Six countries have reported cases of SARS-CoV-2 in farmed minks, including Denmark, the Netherlands, Spain, Sweden, Italy and the US, according to the WHO..
  32. Web site: 12 November 2020. Rapid Risk Assessment: Detection of new SARS-CoV-2 variants related to mink. 12 November 2020. European Centre for Disease Prevention and Control. en.
  33. Web site: Lassaunière. Ria. 11 November 2020. SARS-CoV-2 spike mutations arising in Danish mink and their spread to humans. live. https://web.archive.org/web/20201110135434/https://files.ssi.dk/Mink-cluster-5-short-report_AFO2. 10 November 2020. 11 November 2020. Statens Serum Institut. [...] (hereafter referred to as ΔFVI-spike). [...] These include: i) 69-70deltaHV – a deletion of a histidine and valine at amino acid positions 69 and 70 in the N-terminal domain of the S1 subunit; ii) I692V – a conservative substitution at position 692 that is located seven amino acids downstream of the furin cleavage site; iii) S1147L – a non-conservative substitution at position 1147 in the S2 subunit; and iv) M1229I – a conservative substitution located within the transmembrane domain.
  34. Oude Munnink, B.B.. etal. 2020. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science. 371. 6525. 172–177. 10.1126/science.abe5901. 33172935. 7857398. free.
  35. News: Coronavirus: Denmark imposes lockdowns amid mink covid fears . 5 November 2020 . BBC . 24 December 2020.
  36. News: Prasad. R.. 2020-11-07. No evidence to suggest coronavirus cluster 5 variant found in minks increases virus transmissibility, disease severity. en-IN. The Hindu. 2021-12-04. 0971-751X.
  37. Web site: SARS-CoV-2 mink- associated variant strain – Denmark. 2021-12-04. www.who.int. en.
  38. News: Gorman. James. 4 November 2020. Denmark Will Kill All Farmed Mink, Citing Coronavirus Infections. en-US. The New York Times. 6 November 2020. 0362-4331.
  39. Web site: Pressemøde med Regerigen og SSI . Press meeting with the Government and SSI . DR. 6 November 2020.
  40. Web site: Seruminstituttet bakker op om nedslagtning: Vil undgå nye minkvarianter af coronavirus . The Serum Institute supports slaughter: Will avoid new mink variants of coronavirus. TV2. 7 November 2020.
  41. Web site: Tæt på ni millioner mink i coronaområder er nu aflivet . Close to nine million mink in corona areas have now been killed. Berlignske. 16 November 2020.
  42. News: 4 November 2020. Denmark to cull up to 17 million mink amid coronavirus fears. en-GB. BBC News. 5 November 2020.
  43. Web site: Barrett, Michael. 5 November 2020. How serious is Denmark's mink coronavirus mutation and outbreak?. 6 November 2020. The Local DK.
  44. News: 5 November 2020. Coronavirus: Denmark imposes lockdowns amid mink covid fears. en-GB. BBC News. 6 November 2020.
  45. Web site: Fjordbak, Emma. Her er de nye restriktioner i Nordjylland . Here are the new restrictions in North Jutland. 6 November 2020. TV2. da.
  46. Web site: Mette F. åbner for at løsne restriktioner i Nordjylland før tid . Mette F. opens to loosen restrictions in North Jutland ahead of time . Børsen. 11 November 2020.
  47. Web site: 12 November 2020. Detection of new SARS-CoV-2variants related to mink. 12 November 2020. European Centre for Disease Prevention and Control.
  48. News: Cheng. Maria . 12 November 2020. EU agency: Coronavirus spread in minks could speed mutations. Medical Xpress. 12 November 2020.
  49. Web site: Thousands of mink culled over COVID fears rise from a mass grave in Denmark . CBS News . 27 November 2020 .
  50. Web site: 6 November 2020. Covid: Denmark removed from UK's travel corridor list. 6 November 2020. BBC.
  51. Web site: Coronavirus: UK bans Denmark visitors over mink Covid-19 fears. BBC. 7 November 2020. 7 November 2020 .
  52. News: Murphy. Simon. Beaumont. Peter. 7 November 2020. Travel to UK from Denmark banned amid worries over Covid in mink. en-GB. The Guardian. 7 November 2020. 0261-3077.
  53. Web site: The Health Protection (Coronavirus, International Travel) (England) (Amendment) (No. 27) Regulations 2020 . legislation.gov.uk . 19 February 2021.
  54. News: Erdbrink. Thomas. Santora. Marc. 19 November 2020. The culling of minks in Denmark prompts a political crisis.. The New York Times. live. 27 November 2020. https://web.archive.org/web/20201126210318/https://www.nytimes.com/2020/11/19/world/the-culling-of-minks-in-denmark-prompts-a-political-crisis.html. 26 November 2020.
  55. News: Wamsley. Laurel. 19 November 2020. Danish Agriculture Minister Resigns Amid Criticism For Ordering Mink Cull. NPR. live. 27 November 2020. https://web.archive.org/web/20201126232538/https://www.npr.org/sections/coronavirus-live-updates/2020/11/19/936687145/danish-agriculture-minister-resigns-amid-criticism-for-ordering-mink-cull. 26 November 2020.
  56. News: Wax. Eddy. 18 November 2020. Danish farm minister quits over mink scandal. Politico. live. 27 November 2020. https://web.archive.org/web/20201121064546/https://www.politico.eu/article/danish-farm-minister-mogens-jensen-quits-over-mink-scandal/. 21 November 2020.
  57. Web site: Parliament of Denmark, bill no. 77, 2020–21 session . 21 December 2020 . ft.dk .
  58. Web site: Folketinget (Parliament of Denmark), 2020–21 session, vote no. 170 . 21 December 2020 . ft.dk .
  59. Web site: Bred aftale sikrer fuldstændig erstatning til minkavlere og følgeerhverv . Broad agreement ensures complete compensation for mink breeders and followers . fm.dk . . 26 January 2021 . da.
  60. Web site: Sådan ser minkavlernes erstatning ud: 'De fleste vil få en større erstatning, end de har gæld' . This is what the mink breeders' compensation looks like: 'Most people will receive greater compensation than they have in debt' . DR . 26 January 2021 . 26 January 2021 . da.

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