Cluster 5

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"Cluster 5", also referred to as ΔFVI-spike by the Danish State Serum Institute (SSI), is, or was, a variant of SARS-CoV-2, the virus that causes COVID-19. It was discovered in Northern Jutland, Denmark, and is believed to have been spread from minks to humans via mink farms. On 4 November 2020, it was announced that the mink population in Denmark would be culled to prevent the possible spread of this mutation and reduce the risk of new mutations happening. A lockdown and travel restrictions were introduced in seven municipalities of Northern Jutland to prevent the mutation from spreading, which could compromise national or international responses to the COVID-19 pandemic.

The World Health Organization (WHO) has stated that cluster 5 has a "moderately decreased sensitivity to neutralizing antibodies".[1] SSI warned that the mutation could reduce the effect of COVID-19 vaccines under development, although it was unlikely to render them useless. Following the lockdown and mass-testing, SSI announced on 19 November 2020 that cluster 5 in all probability had become extinct.[2]

Name and mutations

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: cluster 1-5). In cluster 5, also referred to as ΔFVI‑spike by the SSI,[3] 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), and M1229I (methionine to isoleucine at position 1229).[4][3][5]

Mink-related mutations that partially resemble the mutations discovered in Denmark, although part of a separate genomic group, are known from the Netherlands.[6][7]

Background

American mink (Neovison vison)

In 2019, Denmark was the largest producer of mink fur in the world,[8] with the vast majority of the Danish farms located in northern and western Jutland.[9] In recent years the industry had generally been in decline in the country.[10] Along with bats, pangolins, and humans, minks are one of the many mammal species that can be infected with coronaviruses.[11] Transmission of the virus from minks to humans, and mutations related to mink, were first documented in the Netherlands,[6] which prompted the government to bring forward to the end of 2020 a ban on mink farming scheduled to go into effect in 2024.[12] 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.[13] The U.S. Department of Agriculture (USDA) confirmed that cases of minks ill with COVID-19 had been documented in Utah in August 2020.[14] Additional outbreaks have been detected in Michigan, Wisconsin, and Oregon.[15] As of 29 November 2020, COVID-19 infections in mink have been reported in Denmark, Italy, the Netherlands, Spain, Sweden, and the United States.[1][16]

Timeline

Discovery

By 2 November 2020, the Danish state-owned independent research institute Statens Serum Institut (SSI) detected mutated variants of SARS-CoV-2 that humans can be infected by and could have dangerous effects in mink farms of the country with an association between human infections and 191 positive mink farms. They publicly report this on 3 November, calling variants with a known association to three farms "Cluster 5".[17] 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 Northern 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.[5][18][19] Furthermore, the weaker antibody response was shown to reduce immunity acquired by a prior infection.[17] 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.[20]

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).[21][22] To prevent spread of the mutation, it was also announced on 5 November that a lockdown and movement restrictions would be implemented in the Northern Jutland municipalities of Brønderslev, Frederikshavn, Hjørring, Jammerbugt, Læsø, Thisted, and Vesthimmerland effective 6 November,[5][23] 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.[24][25] 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.[26]

The WHO released a statement on the SARS-CoV-2 variants on 6 November.[27] 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.[27] 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.[7][28] In late November, more than 10 million had been culled.[29]

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).[2]

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,[30] Prime Minister Frederiksen acknowledged that the order to cull all minks was illegal, and Jensen resigned on November 18.[31] On December 21, 2020, the government and parliament's left wing parties passed a bill outlawing all mink production throughout 2021.[32] The bill does not contain provisions to remove legal responsibility for the previous culling but does retroactively legalize a bonus payout for swifter cullings.[32] The opposition parties (V, C, O, NB, LA) opposed.[33]

Implications for human health

On 5 November, it was reported that 12 cases of human infection with the cluster 5 variant had been detected.[34]

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.[35] On 7 November, the United Kingdom announced that it will also prohibit entry by non-residents travelling from Denmark, and non-residents who had been to Denmark within the past 14 days. British citizens will still be allowed to return home, but they, as well as all other members of their household, must self-isolate for 14 days. This travel ban was to be reviewed after a week.[36][37][needs update]

See also

References

  1. ^ a b "6 countries find coronavirus at mink farms; fears mutation could hinder vaccine". The Times of Israel. 8 November 2020. Retrieved 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.
  2. ^ a b "De fleste restriktioner læmpes i Nordjylland" [Most restrictions are relaxed in North Jutland]. Sundheds- og Ældreministeriet. 19 November 2020.
  3. ^ a b Lassaunière, Ria (11 November 2020). "SARS-CoV-2 spike mutations arising in Danish mink and their spread to humans". Statens Serum Institut. Archived from the original on 10 November 2020. Retrieved 11 November 2020. [...] (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
  4. ^ "Rapid Risk Assessment: Detection of new SARS-CoV-2 variants related to mink". European Centre for Disease Prevention and Control. 12 November 2020. Retrieved 12 November 2020.
  5. ^ a b c Grove Krause, Tyra. "Mutationer i minkvirus" [Mutations in the mink virus] (in Danish). Statens Serum Institut. Retrieved 6 November 2020.
  6. ^ a b Oude Munnink, B.B.; et al. (2020). "Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans". Science: eabe5901. doi:10.1126/science.abe5901.
  7. ^ a b "Detection of new SARS-CoV-2variants related to mink" (PDF). European Centre for Disease Prevention and Control. 12 November 2020. Retrieved 12 November 2020.
  8. ^ "Denmark to cull up to 17m mink blamed for coronavirus mutation". Financial Times. 4 November 2020.
  9. ^ "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.
  10. ^ "Fakta om minkbranchen i Danmark" [Facts about the mink industry in Denmark]. Danmark's Statistik. 5 November 2020.
  11. ^ Huang, Pien. "Dutch Minks Contract COVID-19 — And Appear To Infect Humans". "All Things Considered". No. 25 June 2020. National Public Radio, Inc. Retrieved 3 October 2020.
  12. ^ "Not fur sale: COVID-19 brings Dutch mink farming to an end". The Economist. No. 5-11 September 2020. The Economist Newspaper Limited.
  13. ^ "FAQ om overvågning og test i mink" [FAQ on monitoring and testing in mink]. Miljø- og Fødevareministeriet.
  14. ^ Cahan, Eli (18 August 2020). "COVID-19 hits U.S. mink farms after ripping through Europe". Science. American Association for the Advancement of Science. Retrieved 3 October 2020.
  15. ^ Alaa Elassar. "An Oregon mink farm has reported a Covid-19 outbreak". CNN. Retrieved 29 November 2020.
  16. ^ "Israelis may be infected with new coronavirus strain from Denmark minks". The Jerusalem Post. 9 November 2020. Retrieved 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.
  17. ^ a b Statens Serum Institut (3 November 2020). "risikovurdering-af-human-sundhed-ved-fortsat-minkavl_03112020.pdf" [risk assessment of human health through continued mink breeding] (PDF) (in Danish). Retrieved 9 December 2020.
  18. ^ Gorman, James (4 November 2020). "Denmark Will Kill All Farmed Mink, Citing Coronavirus Infections". The New York Times. ISSN 0362-4331. Retrieved 6 November 2020.
  19. ^ "Pressemøde med Regerigen og SSI" [Press meeting with the Government and SSI]. DR. 6 November 2020.
  20. ^ "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.
  21. ^ "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.
  22. ^ "Denmark to cull up to 17 million mink amid coronavirus fears". BBC News. 4 November 2020. Retrieved 5 November 2020.
  23. ^ Barrett, Michael (5 November 2020). "How serious is Denmark's mink coronavirus mutation and outbreak?". The Local DK. Retrieved 6 November 2020.
  24. ^ "Coronavirus: Denmark imposes lockdowns amid mink covid fears". BBC News. 5 November 2020. Retrieved 6 November 2020.
  25. ^ Fjordbak, Emma. "Her er de nye restriktioner i Nordjylland" [Here are the new restrictions in North Jutland] (in Danish). TV2. Retrieved 6 November 2020.
  26. ^ "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.
  27. ^ a b "WHO | SARS-CoV-2 mink-associated variant strain – Denmark". WHO. Retrieved 6 November 2020.
  28. ^ Cheng, Maria (12 November 2020). "EU agency: Coronavirus spread in minks could speed mutations". Medical Xpress. Retrieved 12 November 2020.
  29. ^ "Thousands of mink culled over COVID fears rise from a mass grave in Denmark". www.cbsnews.com. 27 November 2020.{{cite web}}: CS1 maint: url-status (link)
  30. ^ Erdbrink, Thomas; Santora, Marc (19 November 2020). "The culling of minks in Denmark prompts a political crisis". The New York Times. Archived from the original on 26 November 2020. Retrieved 27 November 2020.
  31. ^ Wamsley, Laurel (19 November 2020). "Danish Agriculture Minister Resigns Amid Criticism For Ordering Mink Cull". NPR. Archived from the original on 26 November 2020. Retrieved 27 November 2020.
  32. ^ a b Parliament of Denmark, bill no. 77, 2020-21 session, December 21, 2020.
  33. ^ Parliament of Denmark, 2020-21 session, vote no. 170, December 21, 2020
  34. ^ "Coronavirus: Denmark imposes lockdowns amid mink covid fears". www.bbc.co.uk. 5 November 2020. Retrieved 24 December 2020.
  35. ^ "Covid: Denmark removed from UK's travel corridor list". BBC. 6 November 2020. Retrieved 6 November 2020.
  36. ^ "Coronavirus: UK bans Denmark visitors over mink Covid-19 fears". BBC. 7 November 2020. Retrieved 7 November 2020.
  37. ^ Murphy, Simon; Beaumont, Peter (7 November 2020). "Travel to UK from Denmark banned amid worries over Covid in mink". The Guardian. ISSN 0261-3077. Retrieved 7 November 2020.

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